Science.gov

Sample records for anemia disease locus

  1. Anemia in thyroid diseases.

    PubMed

    Szczepanek-Parulska, Ewelina; Hernik, Aleksandra; Ruchała, Marek

    2017-03-28

    Anemia is a frequent, although often underestimated, clinical condition accompanying thyroid diseases. In spite of the fact that anemia and thyroid dysfunction often occur simultaneously, the causative relationship between these two disorders remains ambiguous. Thyroid hormones stimulate erythrocytes precursors proliferation directly, as well as via erythropoietin production enhancement, whereas iron-deficient anemia negatively influences thyroid hormonal status. Thus, different forms of anemia might emerge in the course of thyroid dysfunction. In fact, normocytic anemia is most common, while macrocytic or microcytic anemia occur less frequently. Anemia in hypothyroidism might result from bone marrow depression, decreased erythropoietin production, comorbid diseases, or concomitant iron, vitamin B12 or folate deficiency. Altered iron metabolism and oxidative stress may contribute to anemia in hyperthyroidism. The risk of anemia in autoimmune thyroid disease (AITD) may be posed by pernicious anemia and atrophic gastritis, celiac disease, autoimmune hemolytic syndrome, or rheumatic disorders. The simultaneous occurrence of anemia and thyroid disease, as well as their close relation, make the diseases an important clinical problem. The aim of the study is to provide a comprehensive review summarizing data on the prevalence, potential mechanisms, and therapy of anemia in the course of thyroid diseases from the clinical and pathogenetic perspective. Thyroid dysfunction and autoimmune thyroid disease should be considered in differential diagnosis of treatment-resistant or refractory anemia, as well as in case of increased red blood cell distribution width (RDW). Of note is that the presence of AITD itself, independently from thyroid hormonal status, might affect hemoglobin level.

  2. Anemia in inflammatory bowel disease.

    PubMed

    Giannini, S; Martes, C

    2006-09-01

    Anemia is a frequent extraenteric complication of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis). A systematic review of the literature shows that the overall prevalence of anemia ranges from 8.8% to 73.7% but differs whether in a setting of Crohn's disease or ulcerative colitis. A disabling complication of IBD, anemia worsens the patient's general condition and quality of life, and increases hospitalization rates. Different factors, including vitamin B12 and folic acid deficiency, bone marrow suppression secondary to drug therapy, autoimmune hemolytic anemia and the coexistence of myelodysplastic syndromes are involved in the pathogenesis of anemia in IBD. The main types of anemia in IBD are iron deficiency anemia and anemia accompanying chronic diseases. Correct diagnostic definition of anemia is a fundamental step in guiding the choice of therapeutic options, since the co-presence of different pathogenetic factors may sometimes require a more complex treatment plan. A review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and therapy based on evidence from recent studies is the focus of this article.

  3. The Lbw2 locus promotes autoimmune hemolytic anemia.

    PubMed

    Scatizzi, John C; Haraldsson, Maria K; Pollard, K Michael; Theofilopoulos, Argyrios N; Kono, Dwight H

    2012-04-01

    The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very similar to the corresponding human disease. Previous studies have mapped anti-erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations, including chromosome 4; however, none of these have been analyzed with interval congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2 congenic) mice containing an introgressed fragment of New Zealand White (NZW) on chromosome 4 encompassing Lbw2, a locus previously linked to survival, glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2 congenic mice exhibited marked reductions in AEAs and splenomegaly but not in anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal zone B cells and reduced expansion of peritoneal cells, particularly the B-1a cell subset at early ages, but no reduction in B cell response to LPS. Analysis of a panel of subinterval congenic mice showed that the full effect of Lbw2 on AEA production was dependent on three subloci, with splenomegaly mapping to two of the subloci and expansions of peritoneal cell populations, including B-1a cells to one. These results directly demonstrated the presence of AEA-specific promoting genes on NZB chromosome 4, documented a marked influence of background genes on autoimmune phenotypes related to Lbw2, and further refined the locations of the underlying genetic variants. Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants.

  4. Anemia in Chronic Kidney Disease

    MedlinePlus

    ... ng) per milliliter may mean a person has iron deficiency that requires treatment. 2 The transferrin saturation score ... with kidney disease who have anemia caused by iron, vitamin B12, or folic acid deficiencies to include sources of these nutrients in their ...

  5. Anemia in children with chronic kidney disease

    PubMed Central

    Koshy, Susan M.

    2007-01-01

    Anemia is a common feature of chronic kidney disease, but the management of anemia in children is complex. Erythropoietin and supplemental iron are used to maintain hemoglobin levels. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) clinical practice guidelines for the management of anemia specifically in children were recently published. Pediatric nephrologists are encouraged to use current clinical practice guidelines and best evidence in conjunction with their clinical experience to optimally manage patients with anemia. PMID:17245602

  6. [Anemia in chronic kidney disease].

    PubMed

    Amador-Medina, Lauro Fabián

    2014-01-01

    Anemia is almost unavoidable in the last stages of chronic kidney disease. It is defined as a condition where hemoglobin concentration is below 2 standard deviations from the mean hemoglobin level of the general population, corrected for age and sex (typically, hemoglobin < 13 g/dL in adults and 12 g/dL in women). Although the cause is multi-factorial, the most known is inadequate erythropoietin production. Anemia has been associated with poor prognosis in patients with several conditions such as cancer, chronic kidney disease and congestive heart failure. Treatment with erythropoiesis-stimulating agents, such as erythropoietin, is a logical strategy that has enabled clinical improvement and reduced transfusion requirements for the patients; however, total correction of anemia with erythropoiesis-stimulating agents has demonstrated an increase in the risk of mortality or cardiovascular complications associated with these agents. In randomized trials, the achievement of normal or nearly normal hemoglobin levels is not associated with improved survival and reduced cardiovascular risk; however the ideal hemoglobin level with the use of erythropoiesis-stimulating agents seems to be problematic. More information is needed in order to obtain definite conclusions; in the meantime, using the lowest possible dose of erythropoietin seems to be the most prudent approach.

  7. Iron deficiency anemia in celiac disease.

    PubMed

    Freeman, Hugh James

    2015-08-21

    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet.

  8. Iron deficiency anemia in celiac disease

    PubMed Central

    Freeman, Hugh James

    2015-01-01

    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet. PMID:26309349

  9. Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

    PubMed

    Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

    2016-05-01

    Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

  10. [Anemias in chronic obstructive pulmonary disease].

    PubMed

    Budnevsky, A V; Esaulenko, I E; Ovsyannikov, E S; Zhusina, Yu G

    2016-01-01

    According to different studies, anemia occurs in 8--33% of patients with chronic obstructive pulmonary disease (COPD). The paper describes the most important various causes of anemia in COPD, such as systemic inflammation and endocrine disorders, the use of some medications (theophylline, angiotensin-converting enzyme inhibitors), frequent COPD exacerbations, and long-term oxygen therapy. Lower hemoglobin levels in COPD patients are accompanied by increased shortness of breath, reduced exercise tolerance, and lower quality of life. Furthermore, some investigations have shown that anemia is an independent predictor of death in patients with COPD. In spite of the fact that anemia may be successfully in these patients, the evidence suggesting the importance of its impact on the prognosis of COPD is limited.

  11. [Biermer's disease and autoimmune hemolytic anemia].

    PubMed

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old.

  12. Iron deficiency anemia in inflammatory bowel disease

    PubMed Central

    Kaitha, Sindhu; Bashir, Muhammad; Ali, Tauseef

    2015-01-01

    Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD. PMID:26301120

  13. Inter-ethnic polymorphism of the beta-globin gene locus control region (LCR) in sickle-cell anemia patients.

    PubMed

    Périchon, B; Ragusa, A; Lapouméroulie, C; Romand, A; Moi, P; Ikuta, T; Labie, D; Elion, J; Krishnamoorthy, R

    1993-06-01

    Sequence polymorphisms within the 5'HS2 segment of human locus control region is described among sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat are observed in strong linkage disequilibrium with each of the five major beta s haplotypes. Potential functional relevance of this polymorphic region in globin gene expression is discussed.

  14. Renal Anemia - Risk Factor for Chronic Kidney Disease

    PubMed Central

    Cană-Ruiu, Daniela; Moţa, E.; Istrate, Natalia; Văduva, Cristina; Trican, Eliza

    2013-01-01

    The purpose of this research was to analyze the influence of anemia on renal function in patients with chronic kidney disease. Were monitored for 12 months 165 patients with chronic kidney disease, 96 patients had anemia and a control group of 69 patients had no anemia. A value of hemoglobin under 120 g/L in women and under 130 g/L in men on admission defined anemia. Anemia was associated with a more severe renal damage, a lower residual diuresis, especially in the presence of other risk factors such as diabetes, inflammation or secondary hyperparathyroidism, so early diagnosis and correction of anemia is important for prognosis and evolution of these patients. PMID:24778860

  15. [New insights on hepcidin in anemia of chronic disease].

    PubMed

    Wang, Feng-Dan; Zhou, Dao-Bin

    2009-12-01

    Anemia of chronic disease is normocytic and normochromic. One of the mechanisms is misbalance of iron metabolism. Hepcidin, a kind of protein secreted by liver is considered to be the hormone regulating iron metabolism. It binds to ferroportin and induces the latter one's internalization. Thus, iron transportation from iron storage cells to serum is reduced. Cytokines are elevated in chronic disease. They stimulate hepcidin expression in liver through JAK2/STAT3 pathway. As a result, iron absorption and reabsorption is blocked, which leads to the misbalance of iron metabolism in anemia of chronic disease. In this article, the hepcidin and its relation to iron metabolism and anemia in chronic disease are reviewed.

  16. Anemias.

    PubMed

    Broadway-Duren, Jacqueline B; Klaassen, Hillary

    2013-12-01

    Anemias continue to present a challenge to the health care profession. Anemia is defined as a reduction in one or more of the RBC indices. Patients presenting with a mild form of anemia may be asymptomatic; however, in more serious cases the anemia can become life threatening. In many cases the clinical presentation also reflects the underlying cause. Anemia may be attributed to various causes, whereas autoimmune RBC destruction may be attributed to intrinsic and extrinsic factors. Laboratory tests are essential in facilitating early detection and differentiation of anemia.

  17. Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus

    SciTech Connect

    Papadopoulo, D.; Guillouf, C.; Moustacchi, E. ); Mohrenweiser, H. )

    1990-11-01

    Fanconi anemia (FA) is an inherited human disorder associated with a predisposition to cancer and characterized by anomalies in the processing of DNA cross-links and certain monoadducts. The authors reported previously that the frequency of psoralen-photoinduced mutations at the HPRT locus is lower in FA cells than in normal cells. This hypomutability is shown here to be associated with an increased frequency of deletions in the HPRT gene when either a mixture of cross-links and monoadducts or monoadducts alone are induced. Molecular analysis of mutants in the HPRT gene was carried out. In normal cells the majority of spontaneous and induced mutants are point mutations whereas in FA deletion mutations predominate. In that case a majority of mutants were found to lack individual exons or small clusters of exons whereas in normal cells large (complete or major gene loss) and small deletions are almost equally represented. Thus they propose that the FA defect lies in a mutagenic pathway that, in normal cells, involves by passing lesions and subsequent gap filling by a recombinational process during replication.

  18. [Management of anemia in chronic kidney disease].

    PubMed

    López Gómez, J M

    2008-01-01

    1. All patients with anemia secondary to CKD should be treated and evaluated for possible treatment, irrespective of underlying disease, associated comorbidity or possibility of kidney replacement therapy. 2. In patients treated with ESAs, Hb concentrations should be monitored at least monthly. 3. Hb targets: In all patients with CKD, Hb concentration should be > 11 g/dl and there is no evidence to justify total correction of anemia on a routine basis. Normalization of Hb levels in CKD is associated with an improvement in health-related quality of life, but without differences in mortality or the rate of loss of kidney function (Strength of Recommendation A). 4. Indications for iron therapy: Iron therapy is required in the large majority of patients with CKD treated with ESAs to achieve a Hb equal to or greater than 11 g/dl (Strength of Recommendation B). The recommended serum concentration of ferritin is > 100 mg/dl, which should be associated with a TSI > 20% (Strength of Recommendation C). Iron therapy in patients with CKD can be given orally or intravenously, although the IV route is more effective (Strength of Recommendation A). 5. The initial dose of ESA and its adjustments will depend on the patients clinical condition, baseline Hb levels, the Hb target and the rate of increase in Hb levels observed (Strength of Recommendation C). 6. In all cases and for all ESAs, the subcutaneous route is the recommended route of administration for patients with CKD (Strength of Recommendation C). 7. Resistance to ESAs: A hyporesponse to ESAs is considered to be present when an Hb level of 11 g/dl is not achieved with a dose of epoetin > 300 IU/kg/week or a dose of darbepoetin alpha > 1.5 microg/kg/week (Strength of Recommendation B). 8. There is insufficient evidence in patients with CKD to justify routine use of coadjuvant treatments.

  19. Anemia

    MedlinePlus

    ... a shortage of iron. This condition is called iron deficiency anemia.There are a few other types of ... Try to avoid these foods if you have iron deficiency anemia.Foods high in vitamin B12 include:meat ...

  20. Stimulating erythropoiesis in inflammatory bowel disease associated anemia

    PubMed Central

    Tsiolakidou, Georgia; Koutroubakis, Ioannis E

    2007-01-01

    Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD-associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients. PMID:17828809

  1. Diagnosing anemia in inflammatory bowel disease: beyond the established markers.

    PubMed

    Oustamanolakis, Pantelis; Koutroubakis, Ioannis E; Kouroumalis, Elias A

    2011-10-01

    The main types of anemia in inflammatory bowel disease (IBD) are iron deficiency anemia (IDA) and anemia of inflammatory etiology, or anemia of chronic disease (ACD). In the management of IBD patients with anemia it is essential for the physician to diagnose the type of anemia in order to decide in an evidence-based manner for the appropriate treatment. However, the assessment of iron status in IBD in many cases is rather difficult due to coexistent inflammation. For this assessment several indices and markers have been suggested. Ferritin, seems to play a central role in the definition and diagnosis of anemia in IBD and transferrin, transferrin saturation (Tsat), and soluble transferrin receptors are also valuable markers. All these biochemical markers have several limitations because they are not consistently reliable indices, since they are influenced by factors other than changes in iron balance. In this review, in addition to them, we discuss the newer alternative markers for iron status that may be useful when serum ferritin and Tsat are not sufficient. The iron metabolism regulators, hepcidin and prohepcidin, are still under investigation in IBD. Erythrocytes parameters like the red cell distribution width (RDW) and the percentage of hypochromic red cells as well as reticulocyte parameters such as hemoglobin concentration of reticulocytes, red blood cell size factor and reticulocyte distribution width could be useful markers for the evaluation of anemia in IBD.

  2. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia.

    PubMed

    Ferguson, B J; Skikne, B S; Simpson, K M; Baynes, R D; Cook, J D

    1992-04-01

    Recent studies have shown that the serum transferrin receptor is a sensitive, quantitative measure of tissue iron deficiency. This study was undertaken to determine the serum transferrin receptor's ability to distinguish iron-deficiency anemia from the anemia of chronic inflammation and to identify iron deficiency in patients with liver disease. The mean transferrin receptor level in 17 normal controls was 5.36 +/- 0.82 mg/L compared with 13.91 +/- 4.63 mg/L in 17 patients with iron-deficiency anemia (p less than 0.001). The mean serum receptor level was normal in all 20 patients with acute infection, including five with acute hepatitis, and was also normal in 8 of 10 anemic patients with chronic liver disease. Receptor levels were in the normal range in all but 4 of 41 patients with anemia of chronic disease. We conclude that unlike serum ferritin levels, which are disproportionately elevated in relation to iron stores in patients with inflammation or liver disease, the serum transferrin receptor level is not affected by these disorders and is therefore a reliable laboratory index of iron deficiency anemia.

  3. Anemia of Inflammation and Chronic Disease

    MedlinePlus

    ... AI/ACD may also be advised to take vitamin B12 and folic acid supplements. A person should talk ... and Nutrition People with anemia caused by iron, vitamin B12, or folic acid deficiencies are usually advised to ...

  4. Living with Anemia

    MedlinePlus

    ... Trials Links Related Topics Aplastic Anemia Hemolytic Anemia Iron-Deficiency Anemia Pernicious Anemia Sickle Cell Disease Send a ... Lead poisoning in children has been linked to iron-deficiency anemia . Teenagers also are at risk for anemia, ...

  5. How Is Anemia Diagnosed?

    MedlinePlus

    ... Trials Links Related Topics Aplastic Anemia Hemolytic Anemia Iron-Deficiency Anemia Pernicious Anemia Sickle Cell Disease Send a ... as to the cause of your anemia. In iron-deficiency anemia , for example, red blood cells usually are ...

  6. Anemia Due to Excessive Bleeding

    MedlinePlus

    ... Hemolytic Anemia Hemoglobin C, S-C, and E Diseases Iron Deficiency Anemia Sickle Cell Disease Thalassemias Vitamin Deficiency Anemia ( ... Hemolytic Anemia Hemoglobin C, S-C, and E Diseases Iron Deficiency Anemia Sickle Cell Disease Thalassemias Vitamin Deficiency Anemia ...

  7. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

    PubMed Central

    Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

    2015-01-01

    Abstract Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron. PMID:26061331

  8. Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia.

    PubMed

    Cheng, Pan-pan; Jiao, Xiao-yang; Wang, Xue-hua; Lin, Jing-hua; Cai, Ying-mu

    2011-03-01

    Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.

  9. Anemia

    MedlinePlus

    ... gives the red color to blood. It carries oxygen from the lungs to the rest of the body. Anemia has three main causes: blood loss, lack of red blood cell production, and high rates of red blood cell destruction. ...

  10. Urology and nephrology update: anemia of chronic kidney disease.

    PubMed

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    Anemia is associated with chronic kidney disease (CKD) at all stages, and it is nearly universal among patients with stage 5 CKD. Nonetheless, anemia of CKD is a diagnosis of exclusion. When anemia is detected in a patient with CKD, etiologies other than CKD must be considered and ruled out. Iron deficiency also is common among patients with CKD, and iron replenishment improves the anemia and the response to erythropoiesis-stimulating agents. Current guidelines for managing anemia of CKD recommend a hemoglobin goal of 11 to 12 g/dL, but lower hemoglobin may be acceptable for asymptomatic patients. Some patients do not benefit from erythropoiesis-stimulating agents, or they lose their responsiveness to treatment and transfusions must be considered. Other agents are being investigated as management for anemia of CKD, with vitamin C (ascorbic acid) showing some promise. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  11. Iron Deficiency Anemia: A Common and Curable Disease

    PubMed Central

    Miller, Jeffery L.

    2013-01-01

    Iron deficiency anemia arises when the balance of iron intake, iron stores, and the body's loss of iron are insufficient to fully support production of erythrocytes. Iron deficiency anemia rarely causes death, but the impact on human health is significant. In the developed world, this disease is easily identified and treated, but frequently overlooked by physicians. In contrast, it is a health problem that affects major portions of the population in underdeveloped countries. Overall, the prevention and successful treatment for iron deficiency anemia remains woefully insufficient worldwide, especially among underprivileged women and children. Here, clinical and laboratory features of the disease are discussed, and then focus is placed on relevant economic, environmental, infectious, and genetic factors that converge among global populations. PMID:23613366

  12. Anemia of chronic disease: illness or adaptive mechanism.

    PubMed

    Županić-Krmek; Sučić, Mirna; Bekić, Dinko

    2014-09-01

    The anemia of chronic disease (ACD) is the most prevalent anemia after iron deficiency anemia. It is associated with infectious, inflammatory and neoplastic disease. ACD is a medical condition caused by the release of cytokines which mediate inflammatory and immune response (tumor necrosis factor, interleukins 1 and 6, and interferon). Abnormal iron metabolism with iron trapping in reticuloendothelial cells is primarily the cause of this condition, making iron unavailable for erythropoiesis although iron tissue reserves are elevated. Disorder in erythropoietin secretion and shortening of red cell life span also play a role in the pathogenesis of ACD. The main therapy is treatment of the underlying disorder and red cell transfusions in severe anemia. In more severe (protracted) anemias that lead to impaired quality of life and have an impact on the mortality and survival rate, erythropoiesis stimulating agents are used. Recently, new possibilities are being evaluated in terms of therapy for ACD in defined conditions, such as chelating agents, as well as hepcidin antagonist and other erythropoiesis stimulating agents.

  13. Periodontal disease and anemias associated with Crohn's disease. A case report.

    PubMed

    Nagpal, Swati; Acharya, Anirudh B; Thakur, Srinath L

    2012-03-01

    Crohn's disease (CD) is an inflammatory bowel disease with oral findings, including periodontal manifestations. Anemias, such as iron deficiency and anemia of chronic disease (ACD), are the most common hematologic complications of CD. Periodontitis has systemic effects, and may tend toward anemia, which can be explained by depressed erythropoiesis. In the report presented here, the authors review a case of Crohn's disease diagnosed 10 years previous to the patient presenting with a changing anemic profile and periodontal disease. A discussion of patient and disease management is included.

  14. Characterization and pathogenesis of anemia in glycogen storage disease type Ia and Ib

    PubMed Central

    Wang, David Q.; Carreras, Caroline T.; Fiske, Laurie M.; Austin, Stephanie; Boree, Danielle; Kishnani, Priya S.; Weinstein, David A.

    2013-01-01

    Purpose The aim of this study was to characterize the frequency and causes of anemia in glycogen storage disease type I. Methods Hematologic data and iron studies were available from 202 subjects (163 with glycogen storage disease Ia and 39 with glycogen storage disease Ib). Anemia was defined as hemoglobin concentrations less than the 5th percentile for age and gender; severe anemia was defined as presence of a hemoglobin <10 g/dl. Results In glycogen storage disease Ia, 68/163 patients were anemic at their last follow-up. Preadolescent patients tended to have milder anemia secondary to iron deficiency, but anemia of chronic disease predominated in adults. Severe anemia was present in 8/163 patients, of whom 75% had hepatic adenomas. The anemia improved or resolved in all 10 subjects who underwent resection of liver lesions. Anemia was present in 72% of patients with glycogen storage disease Ib, and severe anemia occurred in 16/39 patients. Anemia in patients with glycogen storage disease Ib was associated with exacerbations of glycogen storage disease enterocolitis, and there was a significant correlation between C-reactive protein and hemoglobin levels (P = 0.036). Conclusion Anemia is a common manifestation of both glycogen storage disease Ia and Ib, although the pathophysiology appears to be different between these conditions. Those with severe anemia and glycogen storage disease Ia likely have hepatic adenomas, whereas glycogen storage disease enterocolitis should be considered in those with glycogen storage disease Ib. PMID:22678084

  15. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  16. Anemia

    MedlinePlus

    ... Adults Making Your Wishes Known Home & Community Home › Aging & Health A to Z › Anemia Font size A A A Print Share Glossary Basic Facts & Information Causes & Symptoms Diagnosis & Tests Care & Treatment Lifestyle & Management Other Resources Caregiving How ...

  17. [Iron deficiency anemia and anemia in chronic celiac disease in children].

    PubMed

    Bel'mer, S V; Mitina, E V; Karpina, L M; Smetanina, N S

    2014-01-01

    Anemia in celiac disease (CD) may be associated with deficiency of iron, vitamins, macro- and micronutrients. It is also possible the development of chronic disease anemia (CDA), associated with activation of proinflammatory cytokines. The aim of this work is to optimize the diagnosis and treatment of celiac disease in children on the basis of study of iron metabolism disorders heterogeneity, including the role of CDA. We observed 34 children with CD aged 1.5 to 17 years, 27 of them children were observed both in the active stage of the disease and in remission. The control group included 25 children aged 1.2 to 17 years who were previously excluded for any chronic (including autoimmune) disease: these children were observed with chronic functional gastrointestinal motility disorders. Special methods of examination were study of iron metabolism, including the determination of the serum hepcidin level, as well as the determination of the serum proinflammatory cytokines (tumor necrosis factor [TNF] -α, interleukin [IL] -2, IL-6, IL-10). In active CD in 14.71% of children anemia of varying severity (mild or moderate) were diagnosed. Among these children we observed mild decrease of serum iron in the range 2.2-8.0 g/ml in 15 of 34 children (44%) and a marked reduction in serum ferritin level in 59% of children. In the active celiac disease in the majority of children there is a decrease in the serum hepcidin, but approximately in 20% of children serum hepcidin level was increased. This indicates the development of CDA in these children. During the active stage the average values of IL-2 was significantly increased (p < 0.05). Thus, the iron metabolism disorders in celiac disease is a result of immunopathological process which results in a reduction in iron absorption in the gut due to the intestinal mucosa villous atrophy and to improve the hepcidin production by liver cells and iron depot blocking with the CDA development in 20% of children.

  18. Inflammation associated anemia and ferritin as disease markers in SLE

    PubMed Central

    2012-01-01

    Introduction In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. Methods A protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed. Results Protein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced. Conclusion Urine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE. PMID:22871034

  19. Anemia and autoimmunity markers in an adolescent with Castleman disease.

    PubMed

    Fretzayas, Andrew; Stasinopoulou, Anastasia; Moustaki, Maria; Stefos, Efstathios; Kaniouras, George; Nicolaidou, Polyxeni

    2015-12-01

    We describe herein the case of an adolescent girl with anemia non-responsive to oral iron, associated with low-grade fever, diminished appetite and fatigue. A palpable mass below the xiphoid was noted. Laboratory findings were consistent with anemia of inflammation. Direct antiglobulin test was positive without any other evidence of autoimmune anemia. Other autoantibodies, such as anti-thyroid and anti-nuclear antibodies, were also positive. After thorough investigation, Castleman disease was the most likely diagnosis on the basis of high serum interleukin (IL)-6 and the magnetic resonance imaging findings. (18)F-FDG positron emission tomography-computed tomography showed a localized hypermetabolic mass, which was resected. Castleman disease of plasma type was identified on histology. Hemogloblin and IL-6 gradually returned to normal, whereas positive autoantibodies became negative. This case emphasizes the need to investigate thoroughly for the underlying cause of anemia of inflammation and to include Castleman disease in the differential diagnosis, on the measurement of IL-6. © 2015 Japan Pediatric Society.

  20. [Health locus of control of patients in disease management programmes].

    PubMed

    Schnee, M; Grikscheit, F

    2013-06-01

    Health locus of control beliefs plays a major role in improving self-management skills of the chronically ill - a main goal in disease management programmes (DMP). This study aims at characterising participants in disease management regarding their health locus of control. Data are based on 4 cross-sectional postal surveys between spring and autumn of 2006 and 2007 within the Health Care Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A high internal locus of control (HLC) occurs significantly less often in DMP patients than in normal chronically ill patients (and healthy people) controlling for age, gender and social class. With increasing age, a high internal locus of control is also significantly less likely. When comparing healthy people, the chronically ill and the DMP participants a social gradient of a high internal locus of control belief can be observed. The weaker internal and higher doctor-related external locus of control of DMP participants should be carefully observed by the physician when trying to strengthen the patients' self-management skills. Evaluators of DMP should take into account the different baselines of DMP patients and relevant control groups and incorporate these differences into the evaluation. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Autoimmune hemolytic anemia terminating seven years later in Hodgkin's disease

    PubMed Central

    Cazenave, Jean-Pierre; Gagnon, Joseph A. E.; Girouard, E.; Bastarache, Alfred

    1973-01-01

    A 64-year-old woman was treated during 7½ years for an isolated AIHA by transfusions, prednisone and splenectomy. The autoantibody was a warm-type IgG with anti-e specificity. At autopsy, generalized Hodgkin's disease of mixed cellularity was found. Only 11 similar cases of hemolytic anemia preceding the development of Hodgkin's disease have been reported in the literature. This association suggests a possible underlying defect in the immune system of the host. PMID:4746134

  2. Microcytic anemia.

    PubMed

    Shine, J W

    1997-05-15

    Because anemia is a condition rather than a disease, an underlying cause must be determined when anemia is identified. Microcytic anemia is a common category of anemia. Iron deficiency anemia is the most common type of microcytic anemia and is also the most common anemia. The clinical presentation of anemia varies according to its severity. Anemias resulting from chronic disease and thalassemia are also relatively common types of microcytic anemia and should be differentiated from iron deficiency to avoid repeated unnecessary trials of iron therapy. Low serum ferritin is the best single laboratory parameter for the diagnosis of iron deficiency. Serum iron, total iron binding capacity and hemoglobin electrophoresis, if necessary, can help differentiate the type of microcytic anemia in patients with normal or elevated levels of serum ferritin. If the evaluation identifies iron deficiency as the type of anemia, the underlying cause must be investigated.

  3. Anemia management in cancer patients with chronic kidney disease.

    PubMed

    Deak, Andras T; Troppan, Katharina; Rosenkranz, Alexander R

    2016-12-01

    Anemia is a common complication of cancer and chronic kidney disease (CKD) associated with decreased physical performance as well as poor prognosis for life expectancy. Renal and cancer-induced anemia share common features regarding pathogenesis and therapeutic strategies. It is typically treated with iron substitution, erythropoiesis-stimulating agents (ESA) and in refractory cases with red blood cell transfusions. However, studies of the past few years unveiled numerous setbacks in the use of ESAs. These included a higher risk of cerebrovascular events and increased mortality without the improvement of cardiovascular outcomes in patients with CKD. Moreover, particularly negative results were observed in patients with previous cancer history under ESA therapy. These unfavorable findings have forced the clinicians to reevaluate the management of renal anemia. This led to decrease of ESA usage, while iron substitution and alternative therapeutic options gained more significance. Iron supplementation is also accompanied with certain risks ranging from gastrointestinal complications to severe allergic reactions and increased rate of infections. Furthermore, the evaluation of the long-term safety of excessive iron therapy is still lacking, especially in CKD patients with cancer. In the absence of these clinical studies, this review aims to summarize the currently available therapeutic strategies in anemia management of CKD patients with concomitant cancer. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  4. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease.

    PubMed

    Panwar, Bhupesh; Gutiérrez, Orlando M

    2016-07-01

    Dysregulated iron homeostasis plays a central role in the development of anemia of chronic kidney disease (CKD) and is a major contributor toward resistance to treatment with erythropoiesis-stimulating agents. Understanding the underlying pathophysiology requires an in-depth understanding of normal iron physiology and regulation. Recent discoveries in the field of iron biology have greatly improved our understanding of the hormonal regulation of iron trafficking in human beings and how its alterations lead to the development of anemia of CKD. In addition, emerging evidence has suggested that iron homeostasis interacts with bone and mineral metabolism on multiple levels, opening up new avenues of investigation into the genesis of disordered iron metabolism in CKD. Building on recent advances in our understanding of normal iron physiology and abnormalities in iron homeostasis in CKD, this review characterizes how anemia related to disordered iron metabolism develops in the setting of CKD. In addition, this review explores our emerging recognition of the connections between iron homeostasis and mineral metabolism and their implications for the management of altered iron status and anemia of CKD. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Iron deficiency anemia in newly diagnosed celiac disease in children.

    PubMed

    Sanseviero, Maria T; Mazza, Giuseppe A; Pullano, Maria N; Oliveiro, Antonella C; Altomare, Federica; Pedrelli, Luca; Dattilo, Bruno; Miniero, Roberto; Meloni, Gianfranco; Giancotti, Laura; Talarico, Valentina

    2016-02-01

    Celiac disease (CD) in children may occur with a wide spectrum of clinical manifestations: anemia is the most frequent extraintestinal manifestation, iron deficiency anemia (IDA) is the common presentation. In our study we aimed to assess IDA condition in a large cohort of pediatric patients with newly diagnosed CD. Our study includes a cohort of 518 children (340 females and 178 males), 6 months-18 years old, joined between January 1990 and January 2013. We have analyzed hematological parameters and iron balance: serum iron, serum ferritin and serum transferrin levels. The diagnosis of IDA was considered on the basis of hemoglobin levels below -2SD, associated with serum iron and ferritin reduction, serum transferrin increase; all compared with the normal reference values for age. Of all patients, 156 patients (30.1%) had anemia, including 103 females (19.8%) and 53 males (10.2%); of these, 112 (21.62%) had IDA (in 18 cases associated with α- or β-thalassemia trait), 22 were thalassemic trait without iron deficiency and the remaining 19 suffered from other forms of anemia. One hundred fifteen patients (22.20%) with low ferritin levels but normal hemoglobin levels were considered as preanemic iron deficient patients. Our data confirm that iron depletion and IDA represent a frequent finding at the diagnosis of CD. This significant relation existing between CD and iron deficiency should be considered by pediatricians at the diagnosis of CD in order to treat the patients.

  6. Sickle cell anemia with moyamoya disease: outcomes after EDAS procedure.

    PubMed

    Fryer, Robert H; Anderson, Richard C; Chiriboga, Claudia A; Feldstein, Neil A

    2003-08-01

    Moyamoya disease is a relatively uncommon neurovascular complication of sickle cell anemia. We report a case series of six patients with sickle cell anemia who developed moyamoya disease and underwent encephaloduroarteriosynangiosis procedures. These six patients presented with either cerebrovascular accidents, transient ischemic attacks, or seizures, and subsequent magnetic resonance imaging scans were suggestive of moyamoya-like changes in the cerebral vasculature. Conventional cerebral angiography was used to confirm the diagnosis in all six patients. Four of six patients manifested a cerebrovascular accident before surgery, and two of these patients were compliant on a transfusion protocol at the time of their cerebrovascular accident. Bilateral (n = 4) or unilateral (n = 2) encephaloduroarteriosynangiosis procedures were performed without any complications. The patient who was stroke-free preoperatively had a cerebrovascular accident 2 weeks after the procedure; otherwise, all patients have remained free of neurovascular complications with an average follow-up of 33 months. Collateral anastomoses between external and internal carotid arteries were established by magnetic resonance angiography in three patients. The encephaloduroarteriosynangiosis procedure is a safe and effective treatment option in patients with sickle cell anemia who develop moyamoya disease.

  7. Anemia in Inflammatory Bowel Disease Outpatients: Prevalence, Risk Factors, and Etiology

    PubMed Central

    Antunes, Carla Valéria de Alvarenga; Hallack Neto, Abrahão Elias; Nascimento, Cristiano Rodrigo de Alvarenga; Chebli, Liliana Andrade; Moutinho, Ivana Lúcia Damásio; Pinheiro, Bruno do Valle; Reboredo, Maycon Moura; Malaguti, Carla; Castro, Antonio Carlos Santana; Chebli, Júlio Maria Fonseca

    2015-01-01

    Anemia is common in inflammatory bowel disease (IBD). However, epidemiological studies of nonwestern IBD populations are limited and may be confounded by demographic, socioeconomic, and disease-related influences. This study evaluated the prevalence, risk factors, and etiology of anemia in Brazilian outpatients with IBD. Methods. In this cross-sectional study, 100 Crohn's disease (CD) patients and 100 ulcerative colitis (UC) subjects were assessed. Anemia workup included complete blood count, ferritin, transferrin saturation, serum levels of folic acid and vitamin B12, and C-reactive protein (CRP) concentration. Results. The overall prevalence of anemia in IBD was 21%. There was no significant difference in the prevalence of anemia between CD subjects (24%) and UC (18%). Moderate disease activity (OR: 3.48, 95% CI, 1.95–9.64, P = 0.002) and elevated CRP levels (OR: 1.8, 95% CI, 1.04–3.11, P = 0.02) were independently associated with anemia. The most common etiologies of anemia found in both groups were iron deficiency anemia (IDA; 10% on CD and 6% on UC) followed by the anemia of chronic disease (ACD; 6% for both groups). Conclusions. In Brazilian IBD outpatients, anemia is highly concurrent condition. Disease moderate activity as well as increased CRP was strongly associated with comorbid anemia. IDA and/or ACD were the most common etiologies. PMID:25705682

  8. Neocytolysis Contributes to the Anemia of Renal Disease

    NASA Technical Reports Server (NTRS)

    Rice, Lawrence; Alfrey, Clarence P.; Driscoll, Theda; Whitley, Carl E.; Hachey, David; Suki, Wadi

    1997-01-01

    Neocytolysis is a recently described physiologic process effecting selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin depression appears to initiate the process, providing rationale to investigate its contributions to the anemia of renal disease. When erythropoietin therapy was withheld, four of five stable hemodialysis patients demonstrated Cr-51 red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these patients received oral (13)C-glycine and (15)N-glycine and showed pathologic enrichment of stool porphyrins by the most recently ingested isotope when EPO therapy was held. This confirms selective hemolysis of newly-released red cells. (One patient had chronic hemolysis by isotope studies of blood and stool.) Thus, neocytolysis can contribute to the anemia of renal disease and explains some unresolved issues about such anemia. One implication is the prediction that intravenous bolus erythropoietin therapy is metabolically and economically inefficient compared to lower doses given more frequently subcutaneously.

  9. Neocytolysis contributes to the anemia of renal disease

    NASA Technical Reports Server (NTRS)

    Rice, L.; Alfrey, C. P.; Driscoll, T.; Whitley, C. E.; Hachey, D. L.; Suki, W.

    1999-01-01

    Neocytolysis is a recently described physiological process affecting the selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin (EPO) depression appears to initiate the process, providing the rationale to investigate its contributions to the anemia of renal disease. When EPO therapy was withheld, four of five stable hemodialysis patients showed chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these four patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of pathological isotope enrichment of stool porphyrins when EPO therapy was held, again supporting selective hemolysis of newly released red cells that take up the isotope (one patient had chronic hemolysis indicated by isotope studies of blood and stool). Thus, neocytolysis can contribute to the anemia of renal disease and explain some unresolved issues about such anemia. One implication is the prediction that intravenous bolus EPO therapy is metabolically and economically inefficient compared with lower doses administered more frequently subcutaneously.

  10. Neocytolysis contributes to the anemia of renal disease

    NASA Technical Reports Server (NTRS)

    Rice, L.; Alfrey, C. P.; Driscoll, T.; Whitley, C. E.; Hachey, D. L.; Suki, W.

    1999-01-01

    Neocytolysis is a recently described physiological process affecting the selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin (EPO) depression appears to initiate the process, providing the rationale to investigate its contributions to the anemia of renal disease. When EPO therapy was withheld, four of five stable hemodialysis patients showed chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these four patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of pathological isotope enrichment of stool porphyrins when EPO therapy was held, again supporting selective hemolysis of newly released red cells that take up the isotope (one patient had chronic hemolysis indicated by isotope studies of blood and stool). Thus, neocytolysis can contribute to the anemia of renal disease and explain some unresolved issues about such anemia. One implication is the prediction that intravenous bolus EPO therapy is metabolically and economically inefficient compared with lower doses administered more frequently subcutaneously.

  11. Brainstem: Neglected Locus in Neurodegenerative Diseases

    PubMed Central

    Grinberg, Lea Tenenholz; Rueb, Udo; Heinsen, Helmut

    2011-01-01

    The most frequent neurodegenerative diseases (NDs) are Alzheimer’s disease (AD), Parkinson’s disease (PD), and frontotemporal lobar degeneration associated with protein TDP-43 (FTLD–TDP). Neuropathologically, NDs are characterized by abnormal intracellular and extra-cellular protein deposits and by disease-specific neuronal death. Practically all terminal stages of NDs are clinically associated with dementia. Therefore, major attention was directed to protein deposits and neuron loss in supratentorial (telencephalic) brain regions in the course of NDs. This was also true for PD, although the pathological hallmark of PD is degeneration of pigmented neurons of the brainstem’s substantia nigra (SN). However, PD pathophysiology was explained by dopamine depletion in the telencephalic basal ganglia due to insufficiency and degeneration of the projection neurons located in SN. In a similar line of argumentation AD- and FTLD-related clinical deficits were exclusively explained by supratentorial allo- and neo-cortical laminar neuronal necrosis. Recent comprehensive studies in AD and PD early stages found considerable and unexpected involvement of brainstem nuclei, which could have the potential to profoundly change our present concepts on origin, spread, and early clinical diagnosis of these diseases. In contrast with PD and AD, few studies addressed brainstem involvement in the course of the different types of FTLD–TDP. Some of the results, including ours, disclosed a higher and more widespread pathology than anticipated. The present review will focus mainly on the impact of brainstem changes during the course of the most frequent NDs including PD, AD, and FTLD–TDP, with special emphasis on the need for more comprehensive research on FTLDs. PMID:21808630

  12. PREFERRED RETINAL LOCUS IN MACULAR DISEASE

    PubMed Central

    GREENSTEIN, VIVIENNE C.; SANTOS, RODRIGO A. V.; TSANG, STEPHEN H.; SMITH, R. THEODORE; BARILE, GAETANO R.; SEIPLE, WILLIAM

    2009-01-01

    Purpose To investigate the location and fixation stability of preferred retinal locations (PRLs) in patients with macular disease, and the relationship among areas of abnormal fundus autofluorescence, the PRL and visual sensitivity. Methods Fifteen patients (15 eyes) were studied. Seven had Stargardt disease, 1 bull’s eye maculopathy, 5 age-related macular degeneration, 1 Best disease, and 1 pattern dystrophy. All tested eyes had areas of abnormal fundus autofluorescence. The PRL was evaluated with fundus photography and the Nidek microperimeter. Visual field sensitivity was measured with the Nidek microperimeter. Results Of the 15 eyes, 4 had foveal and 11 had eccentric fixation. Eccentric PRLs were above the atrophic lesion and their stability did not depend on the degree of eccentricity from the fovea. Visual sensitivity was markedly decreased in locations corresponding to hypofluorescent areas. Sensitivity was not decreased in hyperfluorescent areas corresponding to flecks but was decreased if hyperfluorescence was in the form of dense annuli. Conclusion Eccentric PRLs were in the superior retina in regions of normal fundus autofluorescence. Fixation stability was not correlated with the degree of eccentricity from the fovea. To assess the outcomes of treatment trials it is important to use methods that relate retinal morphology to visual function. PMID:18628727

  13. Diagnosis and treatment of anemia in patients with inflammatory bowel disease

    PubMed Central

    Mücke, Victoria; Mücke, Marcus M.; Raine, Tim; Bettenworth, Dominik

    2017-01-01

    Anemia represents one of the most frequent complications in inflammatory bowel disease (IBD) and severely impairs the quality of life of affected patients. The etiology of anemia in IBD patients can be multifactorial, often involving a combination of iron deficiency (ID) and anemia of chronic disease (ACD). Although current guidelines recommend screening for and treatment of anemia in IBD patients, current observational data suggest that it still remains underdiagnosed and undertreated. Besides basic laboratory parameters (e.g. mean corpuscular volume, reticulocyte count, serum ferritin, transferrin saturation, etc.), the concentration of soluble transferrin receptor (sTfR) and novel parameters such as the sTfR/log ferritin index can guide the challenging task of differentiating between ID and ACD. Once identified, causes of anemia should be treated accordingly. This review summarizes our current understanding of anemia in IBD patients, including the underlying pathology, diagnostic approaches and appropriate anemia treatment regimens. PMID:28042234

  14. [Anemia and iron deficiency in children with chronic respiratory diseases].

    PubMed

    Barja, Salesa; Capo, Eduardo; Briceño, Lilian; Jakubson, Leticia; Méndez, Mireya; Becker, Ana

    2013-01-01

    Children with chronic respiratory disease (CRD) are at increased risk of iron deficiency and anemia, which is under-diagnosed. To describe the iron (Fe) status in children with CRD and to evaluate the effects of its prophylactic indication. Prospective study of children with CRD and adequate Fe intake in the diet. At baseline we measured hemogram, C-reactive protein and Fe profile. Subsequently, those with normal plasma hemoglobin (Hb) were not supplemented with Fe (Group A) and those with iron deficiency anemia or at risk of developing it (group B) were supplemented. We evaluated them 3 months later and, after supplementing all, at 4th month. Of 40 patients, median 30 months old (0.5 to 178), 60% were male, 80% eutrophic. Ventilation or oxygen were required in 45%. Diagnoses: 50% Chronic Lung Damage, 17.5% airway diseases, 10% Bronchopulmonary Dysplasia, 7.5% Cystic Fibrosis and 13.5% other. At baseline 20% were anemic (mostly ferropenic) and 12.5% had an abnormal iron profile. At all, 25 children completed the study: in group A, serum ferritin decreased to 3(th) month (-22.9 ± 30) and incremented to 4(th)month (+12.8 ± 26) μg/L (p = 0.013), without difference in Hb. Group B had a rise in Hb (91 ± 12 to 102 ± 12% of the mean for age, p = 0.04). Anemia and ferropenia are frequent in children with CRD. Decrease of their iron reserves can be prevented if they are supplemented. We suggest monitoring properly and treating early or supplement them prophylactically. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  15. Localization of the congenital dyserythropoietic anemia II locus to chromosome 20q11.2 by genomewide search.

    PubMed Central

    Gasparini, P; Miraglia del Giudice, E; Delaunay, J; Totaro, A; Granatiero, M; Melchionda, S; Zelante, L; Iolascon, A

    1997-01-01

    Congenital dyserythropoietic anemias (CDA) are genetic disorders characterized by anemia and ineffective erythropoiesis. Three main types of CDA have been distinguished: CDA I and CDA III, whose loci have been already mapped, and CDA II (MIM 224100), the most frequent among CDAs, which is transmitted as an autosomal recessive trait and is known also as "HEMPAS" (hereditary erythroblast multinuclearity with positive acidified serum). We have recruited a panel of well-characterized CDA II families and have used them to search for the CDA II gene by linkage analysis. After the exclusion of three candidate genes, we ob-tained conclusive evidence for linkage of CDA II to microsatellite markers on the long arm of chromosome 20 (20q11.2). A maximum two-point LOD score of 5.4 at a recombination fraction of .00 was obtained with marker D20S863. Strong evidence of allelic association with the disease was detected with the same marker. Some recombinational events established a maximum candidate interval of approximately 5 cM. PMID:9345103

  16. Anemia of chronic disease is the more frequent type of anemia seen in patients with chronic idiopathic neutropenia of adults.

    PubMed

    Papadaki, H A; Eliopoulos, D G; Valatas, V; Eliopoulos, G D

    2001-04-01

    This study describes the frequency and the type of anemia seen in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). We found that NI-CINA patients had low hemoglobin levels and increased serum concentrations of erythropoietin (EPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). The hemoglobin levels correlated positively with the number of circulating neutrophils and inversely with the levels of EPO and TNF-alpha but not of IL-1beta. Anemia, defined as the reduction of the hemoglobin below 12.0 g/dl for women and 13.3 g/dl for men, was found in 23 out of 148 patients studied, a proportion of 15.5%. Two of the anemic patients had iron deficiency anemia (8.7%), 11 had anemia of chronic disease (ACD; 47.8%) presenting with normal or slightly reduced erythrocytic indices, low serum iron, and increased serum ferritin, and the remaining ten had anemia of undefined pathogenesis (AUP; 43.5%) with normal or slightly decreased erythrocytic indices, serum iron ranging from 43 to 88 microg/dl, and ferritin values ranging from 12 to 50 ng/ml. We conclude that ACD is the more frequent type of anemia seen in patients with NI-CINA, and that pro-inflammatory cytokines, notably TNF-alpha, may be involved in the pathogenesis of both ACD and AUP, given that serum levels of the cytokine were significantly increased and that the EPO response to anemia was blunted in these patients. These findings further support our previously reported suggestion for the possible existence, in NI-CINA patients, of an unrecognized low-grade chronic inflammatory process that may be involved in the pathogenesis of the disorder.

  17. 'Locus of control', health-related quality of life, emotional distress and disability in Parkinson's disease.

    PubMed

    Rizza, Federica; Gison, Annalisa; Bonassi, Stefano; Dall'Armi, Valentina; Tonto, Francesca; Giaquinto, Salvatore

    2017-06-01

    This cross-sectional study evaluated locus of control and its subscales in Parkinson's disease. A total of 50 consecutive Parkinson's disease participants and 50 healthy volunteers (control group) were enrolled. External locus of control was significantly higher in Parkinson's disease participants, whereas internal locus of control had no significant differences. External locus of control and internal locus of control were correlated in control group, but not in Parkinson's disease. In Parkinson's disease participants, external locus of control was negatively associated with health-related quality of life as well as positively associated with emotional distress and disease severity (but not with disability). After adjusting to confound variables, the associations remained. On the other hand, internal locus of control was negatively associated with depression.

  18. The prevalence of celiac disease in children with iron-deficiency anemia.

    PubMed

    Ertekin, Vildan; Tozun, Mahya Sultan; Küçük, Nuran

    2013-01-01

    Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. Iron-deficiency anemia is the most commonly encountered anemia in humans. Iron-deficiency anemia also is a common extraintestinal manifestation of celiac disease. To determine the celiac disease prevalence in children with iron-deficiency anemia and to compare the hematologic parameters in iron-deficiency anemia patients with and without celiac disease. A total of 61 patients aged 2-16 years who presented with iron-deficiency anemia were included in this study. Hemoglobin, red cell indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width), serum iron, and serum ferritin were determined. Venous blood samples for anti-tissue transglutaminase antibody immunoglobuline A were obtained from these patients. Upper gastrointestinal endoscopy was recommended to patients who had positive serology. Of 61 patients with iron-deficiency anemia, 13 (21,3%) had positive serology for celiac disease. The small intestine biopsy of all patients with positive serology showed villous atrophy (Marsh 3). The mean hemoglobin level was significantly lower in iron-deficiency anemia patients with celiac disease when compared to those without celiac disease (7,8±2,6 vs. 11,3±0,9 g/dL, p>0,05). There was a statistically significant negative correlation of tissue transglutaminase titers with hemoglobin, red cell indices, serum iron, and serum ferritin levels. Screening of celiac disease by anti-tissue transglutaminase antibody should be done as a routine investigation in children with iron-deficiency anemia. Biopsy should be recommended in patients with iron-deficiency anemia who have positive celiac disease serology.

  19. [Mecobalamin improved pernicious anemia in an elderly individual with Hashimoto's disease and diabetes mellitus].

    PubMed

    Izumi, Kenichi; Fujise, Takehiro; Inoue, Kanako; Mori, Hitoe; Yamazaki, Kouta; Hongou, Yui; Takagi, Satoko; Yamanouchi, Hiroko; Ashida, Kenji; Anzai, Keizo

    2013-01-01

    A 73-year-old Japanese man with Hashimoto's disease and diabetes mellitus received regular medical checkups for type 2 diabetes care. Blood tests indicated macrocytic anemia (red blood cell count, 279×104 /μL; hemoglobin, 12.2 g/dL; hematocrit, 34.0%; mean corpuscular volume, 121.9 fL). The laboratory data demonstrated a normal folic acid level with a low vitamin B12 level. An endoscopic examination indicated no signs of gastric or intestinal bleeding. Positive results for anti-intrinsic factor antibodies were strongly suggestive of pernicious anemia. The patient refused cobalamin injections to treat the anemia. However, the oral administration of mecobalamin for the treatment of diabetic neuropathy was simultaneously initiated. Subsequently, the anemia gradually improved. Oral mecobalamin was presumably effective for pernicious anemia management. Anemia is frequently observed in elderly patients, and the incidence of pernicious anemia increases with age. Anemia is conventionally treated with cobalamin injections. Currently, the oral administration of mecobalamin is not the typical treatment for anemia. However, as in our case, a few reports have documented positive results following oral mecobalamin treatment. Moreover, oral mecobalamin is a fairly recent, novel, noninvasive mode of treatment, making it ideal for elderly patients, who are generally frail. This case suggests the efficacy of mecobalamin for the treatment of pernicious anemia.

  20. Clinical considerations and practical recommendations for the primary care practitioner in the management of anemia of chronic kidney disease.

    PubMed

    Basile, Jan N

    2007-12-01

    Anemia is prevalent in patients with chronic kidney disease (CKD) and is a risk factor for poor disease outcome. Anemia acts as a risk multiplier, significantly increasing the risk of death in anemic versus nonanemic CKD patients with similar comorbidities. Erythropoiesis-stimulating agents (ESA) are a mainstay for the treatment of anemia in renal patients on dialysis, but recent data suggests that earlier treatment of anemia in CKD may delay the onset of end-stage renal disease (ESRD) and decrease mortality. Nonetheless, anemia of CKD is under-recognized and undertreated during the period before initiation of dialysis, when anemia correction may have the greatest impact on disease outcome. This report describes anemia in CKD and its association with diabetes, cardiovascular disease, and poor disease outcome, and offers suggestions for the recognition and treatment of anemia of CKD in the primary care setting.

  1. The Significance of Serum Transferrin Receptor Levels in the Diagnosis of the Coexistence of Anemia of Chronic Disease and Iron Deficiency Anemia

    PubMed Central

    Yokus, Osman; Yilmaz, Bilal; Albayrak, Murat; Balcik, Ozlem Sahin; Helvaci, Mehmet Rami; Sennaroglu, Engin

    2011-01-01

    Objective: Iron deficiency anemia is the most common cause of microcytic anemia throughout the world. Ferritin levels are good indicators of iron stores; however, levels may increase irrespective of iron stores in cases of chronic disease. Therefore, it is difficult to diagnose iron deficiency anemia coexisting with anemia of chronic disease. Materials and Methods: To determine the level of transferrin receptor in subjects, 30 patients with iron deficiency anemia, 30 patients with anemia of chronic disease and 30 patients with both diseases were included in the study. Results: Mean serum transferrin receptor levels were 5.99±2.98 mg/L in the iron deficiency anemia group, 1.90±1.15 mg/L in the anemia of chronic disease group and 3.07±0.90 mg/L in the combination group. Comparing groups with each other revealed significant differences (p<0.05). Conclusion: It is concluded that the assessment of serum transferrin receptor levels is a useful method for the diagnosis of iron deficiency anemia in patients. PMID:25610152

  2. The significance of serum transferrin receptor levels in the diagnosis of the coexistence of anemia of chronic disease and iron deficiency anemia.

    PubMed

    Yokus, Osman; Yilmaz, Bilal; Albayrak, Murat; Balcik, Ozlem Sahin; Helvaci, Mehmet Rami; Sennaroglu, Engin

    2011-04-01

    Iron deficiency anemia is the most common cause of microcytic anemia throughout the world. Ferritin levels are good indicators of iron stores; however, levels may increase irrespective of iron stores in cases of chronic disease. Therefore, it is difficult to diagnose iron deficiency anemia coexisting with anemia of chronic disease. To determine the level of transferrin receptor in subjects, 30 patients with iron deficiency anemia, 30 patients with anemia of chronic disease and 30 patients with both diseases were included in the study. Mean serum transferrin receptor levels were 5.99±2.98 mg/L in the iron deficiency anemia group, 1.90±1.15 mg/L in the anemia of chronic disease group and 3.07±0.90 mg/L in the combination group. Comparing groups with each other revealed significant differences (p<0.05). It is concluded that the assessment of serum transferrin receptor levels is a useful method for the diagnosis of iron deficiency anemia in patients.

  3. [Sickle cell anemia causes varied symptoms and high morbidity. Serious prognosis in the most common genetic disease in the world].

    PubMed

    Kjellander, Christian; Sennström, Maria K B; Stiller, Viveka; Ågren, Anna

    2015-03-03

    Sickle cell anemia is a life-threatening disease, and the most common genetic disease in the world. The prevalence of sickle cell anemia in Sweden is unknown. Sickle cell anemia is an important disease, because of its variable complications, in many medical and surgical specialties. The overview highlights common medical problems encountered in sickle cell anemia presented through a case report of a pregnant woman.

  4. [Pernicious anemia and autoimmune thyroid diseases in elderly people].

    PubMed

    Velarde-Mayol, Cristina; de la Hoz-García, Benito; del Cañizo-Fernández-Roldán, Carlos; Hernández-López, Alba Marina; Loza-Candia, Isabel; Cardona-Hernández, Andrea

    2015-01-01

    Autoimmune thyroid diseases (ATD), and pernicious anemia (PA) in particular, are common in elderly people. The relationship between both of these is currently being discussed. The objective of this study is to determine the correlation between ATD and PA in elderly people, and if there are other associated factors affecting this relationship. The factors studied to analyse this association were social-health variables, autoimmune comorbidity (type 1 diabetes and other autoimmune diseases), the taking of drugs that alter vitamin B12 levels (Metformin and protein bomb inhibitors), and the chronological order in which both diseases appear in this population. A logistic regression analysis was performed to determine which of the described variables could have an on both diseases. The prevalence was 8.2% for ATD and 3.3% for PA, with a progressive increase in the annual incidence in the past 10 years from 7.1 to 12.7 cases per 1,000 persons>65 years for ATI, and from 1.6 to 7.4 cases for PA. PA was found in 18.6% of the patients with ATD, and the 45% of PA presented with ATD, mainly in women (RR=6.0). The average time in diagnosing the second disease was about 8 years. When there was a third autoimmune disease the likelihood of ATD and PA increased fourfold. Patients with ATD and consuming drugs which were affecting the absorption of vitamin B12 had double the probability of developing a PA compared with those who were not taking medications. The results of this study confirm the association between ATI and AP among people 65 or older, also a progressive increase in the incidence of these diseases. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

  5. Anemia in inflammatory bowel disease: A neglected issue with relevant effects

    PubMed Central

    Guagnozzi, Danila; Lucendo, Alfredo J

    2014-01-01

    Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients. PMID:24707137

  6. Anemia in inflammatory bowel disease: a neglected issue with relevant effects.

    PubMed

    Guagnozzi, Danila; Lucendo, Alfredo J

    2014-04-07

    Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients.

  7. Iron-deficiency anemia as a subclinical celiac disease presentation in an Argentinian population.

    PubMed

    Lasa, J S; Olivera, P; Soifer, L; Moore, R

    There is a wide heterogeneity in the reports of celiac disease prevalence in iron-deficiency anemia patients. To determine the prevalence of celiac disease in patients with iron-deficiency anemia. Adult patients with a diagnosis of iron-deficiency anemia were enrolled for upper endoscopy with duodenal biopsies. Healthy volunteers that underwent upper endoscopy were enrolled as controls. A total of 135 patients with iron-deficiency anemia and 133 controls were enrolled. Celiac disease prevalence was higher in the iron-deficiency anemia group [11.11 vs. 1.51%, OR: 8.18 (1.83-36.55), P=.001). Of the celiac disease patients in the iron-deficiency anemia group, 73.3% had at least one endoscopic sign suggesting villous atrophy, whereas 100% of the celiac disease patients in the control group presented with at least one endoscopic sign. Patients with iron-deficiency anemia have an increased risk for celiac disease. Up to 25% of these patients may not present any endoscopic sign suggesting villous atrophy. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Sideroblastic anemia as a preleukemic event in patients treated for Hodgkin's disease

    SciTech Connect

    Kitahara, M.; Cosgriff, T.M.; Eyre, H.J.

    1980-05-01

    Sideroblastic anemia after treatment for Hodgkin's disease was seen in two patients 3 years after completion of radiation therapy and chemotherapy. This was followed in both by the development of myelomonoblastic leukemia. No evidence of recurrent Hodgkin's disease was present in either patient. Our observation suggests that development of sideroblastic anemia in patients previously treated for Hodgkin's disease is probably secondary to the treatment and is a preleukemic event.

  9. [The prevalence and characteristics of anemia in Crohn's disease in the Chinese].

    PubMed

    Tang, Rui-han; Chao, Kang; Zhang, Sheng-hong; Chen, Bai-li; He, Yao; Gao, Xiang; Zeng, Zhi-rong; Hu, Pin-jin; Chen, Min-hu

    2013-05-01

    To investigate the prevalence and characteristics of anemia among patients with Crohn's disease (CD) in Chinese population and identify the possible risk factors. A cross-sectional study was performed in 441 patients with CD enrolled from the First Affiliated Hospital of Sun Yat-Sen University between January 2003 and May 2012. The prevalence, severity, type of anemia in these patients was assessed when diagnosis was confirmed. A multivariate logistic regression including 122 patients was performed to screen risk factors of anemia. The prevalence of anemia was 64.4% (284/441) with 69.0% (196/284) mild anemia, 28.9% (82/284) moderate anemia and 2.1% (6/284) severe anemia. The most common morphological classification was hypochromic microcytic anemia (43.7%, 124/284). Multivariate logistic regression showed the predictive factors for anemia were higher levels of modified Crohn's disease activity index (CDAI) (OR = 1.007, 95% CI 1.002-1.013), platelet count (OR = 1.007, 95% CI 1.001-1.012), erythrocyte sedimentation rate (OR = 1.024, 95% CI 1.000-1.048), penetrating behavior (OR = 16.952, 95% CI 2.626-108.626), structuring behavior (OR = 6.717, 95% CI 1.583-28.507), older age at diagnosis (OR = 1.065, 95% CI 1.012-1.121),and lower body mass index (BMI) (OR = 0.769, 95% CI 0.633-0.935). Anemia is a common complication in patients with CD among Chinese population. Activity of the underlying disease, older age at diagnosis, penetrating or structuring disease behavior and low BMI are the risk factors.

  10. Multipoint mapping of the central core disease locus

    SciTech Connect

    Schwemmle, S.; Wolff, K.; Grimm, T.; Mueller, C.R. ); Palmucci, L.M. ); Lehmann-Horn, F. ); Huebner, Ch. ); Hauser, E. ); Iles, D.E. ); MacLennan, D.H. )

    1993-07-01

    A linkage analysis with 12 DNA markers from proximal 19q was performed in eight families with central core disease (CCO). Two-point analysis gave a peak lod score of Z = 4.95 at [theta] = 0.00 for the anonymous marker D19S190 and of Z = 2.53 at [theta] = 0.00 for the ryanodine receptor (RYR1) candidate gene. Multipoint linkage data place the CCO locus at 19q13.1, flanked proximally by D19S191/D19S28 and distally by D19S47. This map location includes the RYR1 gene. The results of the linkage study present no evidence for genetic heterogeneity of CCO. 19 refs., 2 figs., 1 tab.

  11. Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

    PubMed Central

    Shaw, Julia G.; Friedman, Jennifer F.

    2011-01-01

    Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed. PMID:21738863

  12. Prevalence of Anemia in Chronic Kidney Disease in the United States

    PubMed Central

    Stauffer, Melissa E.; Fan, Tao

    2014-01-01

    Anemia is one of the many complications of chronic kidney disease (CKD). However, the current prevalence of anemia in CKD patients in the United States is not known. Data from the National Health and Nutrition Examination Survey (NHANES) in 2007–2008 and 2009–2010 were used to determine the prevalence of anemia in subjects with CKD. The analysis was limited to adults aged >18 who participated in both the interview and exam components of the survey. Three outcomes were assessed: the prevalence of CKD, the prevalence of anemia in subjects with CKD, and the self-reported treatment of anemia. CKD was classified into 5 stages based on the glomerular filtration rate and evidence of kidney damage, in accordance with the guidelines of the National Kidney Foundation. Anemia was defined as serum hemoglobin levels ≤12 g/dL in women and ≤13 g/dL in men. We found that an estimated 14.0% of the US adult population had CKD in 2007–2010. Anemia was twice as prevalent in people with CKD (15.4%) as in the general population (7.6%). The prevalence of anemia increased with stage of CKD, from 8.4% at stage 1 to 53.4% at stage 5. A total of 22.8% of CKD patients with anemia reported being treated for anemia within the previous 3 months–14.6% of patients at CKD stages 1–2 and 26.4% of patients at stages 3–4. These results update our knowledge of the prevalence and treatment of anemia in CKD in the United States. PMID:24392162

  13. Managing dialysis patients who develop anemia caused by chronic kidney disease: focus on peginesatide.

    PubMed

    Valliant, Amanda; Hofmann, R Michael

    2013-01-01

    Anemia in chronic kidney disease is a prevalent and expensive problem in the United States, and it is well documented that anemia worsens as glomerular filtration rates decline. The complications of severe anemia in this patient population contribute significantly to their overall morbidity with increased cardiovascular complications, decreased quality of life, and increased dependence on transfusions to maintain adequate hemoglobin levels. Erythropoietin-stimulating agents (ESAs) have revolutionized the treatment of anemia in this population, but there has been a great deal of controversy surrounding the quest for the ideal hemoglobin target. In addition, there are economic and practice management implications where anemia treatment is concerned, with ongoing refinement of Centers for Medicare and Medicaid Services-bundled payments. One of the newest additions to the arsenal used to fight anemia in end-stage renal disease patients is peginesatide (Omontys), a synthetic, PEGylated, peptide-based ESA that acts by stimulating the erythropoietin receptor. The role of peginesatide in the future treatment of anemia in chronic kidney disease remains uncertain, with new safety concerns being brought to attention as it emerges on the market, prompting a national recall.

  14. Managing dialysis patients who develop anemia caused by chronic kidney disease: focus on peginesatide

    PubMed Central

    Valliant, Amanda; Hofmann, R Michael

    2013-01-01

    Anemia in chronic kidney disease is a prevalent and expensive problem in the United States, and it is well documented that anemia worsens as glomerular filtration rates decline. The complications of severe anemia in this patient population contribute significantly to their overall morbidity with increased cardiovascular complications, decreased quality of life, and increased dependence on transfusions to maintain adequate hemoglobin levels. Erythropoietin-stimulating agents (ESAs) have revolutionized the treatment of anemia in this population, but there has been a great deal of controversy surrounding the quest for the ideal hemoglobin target. In addition, there are economic and practice management implications where anemia treatment is concerned, with ongoing refinement of Centers for Medicare and Medicaid Services-bundled payments. One of the newest additions to the arsenal used to fight anemia in end-stage renal disease patients is peginesatide (Omontys), a synthetic, PEGylated, peptide-based ESA that acts by stimulating the erythropoietin receptor. The role of peginesatide in the future treatment of anemia in chronic kidney disease remains uncertain, with new safety concerns being brought to attention as it emerges on the market, prompting a national recall. PMID:24023516

  15. Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease.

    PubMed

    Yu, Ivarosa Bing-Ye; Huang, Hui-Pi

    2016-01-01

    In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA) class IV HF (33.3%), followed by classes III (15.2%) and II (0%; p < 0.001). The presence of anemia was associated with HF severity and blood creatinine > 1.6 mg/dL (both p < 0.001). Anemic dogs had a shorter median survival [13 months; 95% confidence interval (CI): 0.7-19.1] than nonanemic dogs (28 months; 95% CI: 15.3-40.7; p < .001). NYHA class IV (hazard ratio (HR): 3.1, 95% CI: 2.2-4.3; p < 0.001), left atrium/aorta ratio > 1.7 (HR: 2.7, 95% CI: 1.7-4.2; p = 0.001), and presence of anemia (HR: 1.43, 95% CI: 1.1-1.9; p = 0.004) emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD.

  16. Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease

    PubMed Central

    Yu, Ivarosa Bing-Ye

    2016-01-01

    In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA) class IV HF (33.3%), followed by classes III (15.2%) and II (0%; p < 0.001). The presence of anemia was associated with HF severity and blood creatinine > 1.6 mg/dL (both p < 0.001). Anemic dogs had a shorter median survival [13 months; 95% confidence interval (CI): 0.7–19.1] than nonanemic dogs (28 months; 95% CI: 15.3–40.7; p < .001). NYHA class IV (hazard ratio (HR): 3.1, 95% CI: 2.2–4.3; p < 0.001), left atrium/aorta ratio > 1.7 (HR: 2.7, 95% CI: 1.7–4.2; p = 0.001), and presence of anemia (HR: 1.43, 95% CI: 1.1–1.9; p = 0.004) emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD. PMID:27840827

  17. Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.

    PubMed

    Astuti, Dewi; Sabir, Ataf; Fulton, Piers; Zatyka, Malgorzata; Williams, Denise; Hardy, Carol; Milan, Gabriella; Favaretto, Francesca; Yu-Wai-Man, Patrick; Rohayem, Julia; López de Heredia, Miguel; Hershey, Tamara; Tranebjaerg, Lisbeth; Chen, Jian-Hua; Chaussenot, Annabel; Nunes, Virginia; Marshall, Bess; McAfferty, Susan; Tillmann, Vallo; Maffei, Pietro; Paquis-Flucklinger, Veronique; Geberhiwot, Tarekign; Mlynarski, Wojciech; Parkinson, Kay; Picard, Virginie; Bueno, Gema Esteban; Dias, Renuka; Arnold, Amy; Richens, Caitlin; Paisey, Richard; Urano, Fumihiko; Semple, Robert; Sinnott, Richard; Barrett, Timothy G

    2017-07-01

    We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org. © 2017 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

  18. Advancing a vaccine to prevent hookworm disease and anemia.

    PubMed

    Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia M; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-03

    A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm infection and anemia caused by Necator americanus. It is intended for use in low- and middle-income countries where hookworm is highly endemic and responsible for at least three million disability-adjusted life years. So far, the human hookworm vaccine is being developed in the non-profit sector through the Sabin Vaccine Institute Product Development Partnership (PDP), in collaboration with the HOOKVAC consortium of European and African partners. We envision the vaccine to be incorporated into health systems as part of an elimination strategy for hookworm infection and other neglected tropical diseases, and as a means to reduce global poverty and address the Sustainable Development Goals. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  19. The deadly triangle of anemia, renal insufficiency, and cardiovascular disease: implications for prognosis and treatment.

    PubMed

    McCullough, Peter A; Lepor, Norman E

    2005-01-01

    Recently there has been considerable interest in the associations between blood hemoglobin (Hb) level, renal function, and cardiovascular disease. Anemia is a common feature of end-stage renal disease, but it also accompanies lesser degrees of chronic kidney disease (CKD). The degree of anemia roughly approximates the severity of CKD. Anemia seen in diabetes has been linked to diabetic nephropathy; however, diabetes itself affects the hematologic system in several ways. Anemia is associated with left ventricular hypertrophy, cardiovascular morbidity, progressive loss of kidney function, and poor quality of life. Anemia seems to act as a mortality multiplier; that is, at every decrease in Hb below 12 g/dL, mortality increases in patients with CKD, cardiovascular disease, and those with both. Unlike blood transfusion, treatment of anemia with exogenous erythropoietin in patients with cardiorenal disease has shown promise in reducing morbidity and in improving survival and quality of life. Increasing the Hb level from less than 10 g/dL to 12 g/dL has resulted in favorable changes in left ventricular remodeling, improved ejection fraction, improved functional classification, and higher levels of peak oxygen consumption with exercise testing. Clinical trials are underway to test the role of erythropoietin in patients with CKD and in patients with heart failure.

  20. Fanconi Anemia Research Fund

    MedlinePlus

    ... Support Publications Fundraising News What is the Fanconi Anemia Research Fund? Fanconi anemia is an inherited disease that can lead to ... population. Lynn and Dave Frohnmayer started the Fanconi Anemia Research Fund, in 1989 to find effective treatments ...

  1. Cooley's Anemia Foundation

    MedlinePlus

    ... role in their lives. Welcome to the Cooley's Anemia Foundation Website The Cooley's Anemia Foundation is dedicated to serving people afflicted with ... major form of this genetic blood disease, Cooley's anemia/thalassemia major. Our mission is advancing the treatment ...

  2. Who Is at Risk for Anemia?

    MedlinePlus

    ... Trials Links Related Topics Aplastic Anemia Hemolytic Anemia Iron-Deficiency Anemia Pernicious Anemia Sickle Cell Disease Send a ... babies are at risk for anemia because of iron deficiency. At-risk infants include those who are born ...

  3. Hematologic manifestations of systemic disease (including iron deficiency, anemia of inflammation and DIC).

    PubMed

    Witmer, Char M

    2013-12-01

    A complete blood cell count (CBC) is a frequent test sent to aid in the diagnostic evaluation of ill patients. Not uncommonly hematologic abnormalities may be the first sign of an underlying systemic disorder. The astute clinician needs to understand how systemic disease can affect the CBC to direct further diagnostic investigations. This article focuses on the 2 most common acquired anemias including iron deficiency and anemia of inflammation as well as disseminated intravascular coagulation.

  4. Prevalence of high blood pressure, heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia among the UAE adolescent population.

    PubMed

    Barakat-Haddad, Caroline

    2013-01-01

    This study examined the prevalence of high blood pressure, heart disease, and medical diagnoses in relation to blood disorders, among 6,329 adolescent students (age 15 to 18 years) who reside in the United Arab Emirates (UAE). Findings indicated that the overall prevalence of high blood pressure and heart disease was 1.8% and 1.3%, respectively. Overall, the prevalence for thalassemia, sickle-cell anemia, and iron-deficiency anemia was 0.9%, 1.6%, and 5%, respectively. Bivariate analysis revealed statistically significant differences in the prevalence of high blood pressure among the local and expatriate adolescent population in the Emirate of Sharjah. Similarly, statistically significant differences in the prevalence of iron-deficiency anemia were observed among the local and expatriate population in Abu Dhabi city, the western region of Abu Dhabi, and Al-Ain. Multivariate analysis revealed the following significant predictors of high blood pressure: residing in proximity to industry, nonconventional substance abuse, and age when smoking or exposure to smoking began. Ethnicity was a significant predictor of heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia. In addition, predictors of thalassemia included gender (female) and participating in physical activity. Participants diagnosed with sickle-cell anemia and iron-deficiency anemia were more likely to experience different physical activities.

  5. Prevalence of High Blood Pressure, Heart Disease, Thalassemia, Sickle-Cell Anemia, and Iron-Deficiency Anemia among the UAE Adolescent Population

    PubMed Central

    Barakat-Haddad, Caroline

    2013-01-01

    This study examined the prevalence of high blood pressure, heart disease, and medical diagnoses in relation to blood disorders, among 6,329 adolescent students (age 15 to 18 years) who reside in the United Arab Emirates (UAE). Findings indicated that the overall prevalence of high blood pressure and heart disease was 1.8% and 1.3%, respectively. Overall, the prevalence for thalassemia, sickle-cell anemia, and iron-deficiency anemia was 0.9%, 1.6%, and 5%, respectively. Bivariate analysis revealed statistically significant differences in the prevalence of high blood pressure among the local and expatriate adolescent population in the Emirate of Sharjah. Similarly, statistically significant differences in the prevalence of iron-deficiency anemia were observed among the local and expatriate population in Abu Dhabi city, the western region of Abu Dhabi, and Al-Ain. Multivariate analysis revealed the following significant predictors of high blood pressure: residing in proximity to industry, nonconventional substance abuse, and age when smoking or exposure to smoking began. Ethnicity was a significant predictor of heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia. In addition, predictors of thalassemia included gender (female) and participating in physical activity. Participants diagnosed with sickle-cell anemia and iron-deficiency anemia were more likely to experience different physical activities. PMID:23606864

  6. Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease

    PubMed Central

    Torino, Ana Beatriz Barbosa; Gilberti, Maria de Fátima Pererira; da Costa, Edvilson; de Lima, Gisélia Aparecida Freire; Grotto, Helena Zerlotti Wolf

    2015-01-01

    Objective The aim of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters to identify three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency. Methods Peripheral blood cells from 117 adult patients with anemia were classified according to iron status, inflammation, and hemoglobinopathies as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β-thalassemia (n = 25). The percentage of microcytic erythrocytes, hypochromic erythrocytes, and the levels of hemoglobin in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating anemia. Results There was no difference between the groups of iron deficiency and anemia of chronic disease associated with absolute iron deficiency for any of the parameters. The percentage of hypochromic erythrocytes was the best parameter to identify absolute iron deficiency in patients with anemia of chronic disease (area under curve = 0.785; 95% confidence interval: 0.661–0.909 with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic erythrocyte count minus hypochromic erythrocyte count was very accurate to differentiate iron deficiency anemia from heterozygous β-thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005 with a sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8). Conclusion The erythrocyte and reticulocyte indices are moderately good to identify absolute iron deficiency in patients with anemia of chronic disease. PMID:25818816

  7. Evaluation of red cell and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease

    PubMed Central

    Torino, Ana Beatriz Barbosa; Gilberti, Maria de Fátima Pererira; da Costa, Edvilson; de Lima, Gisélia Aparecida Freire; Grotto, Helena Zerlotti Wolf

    2014-01-01

    Objective The purpose of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters under three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency. Methods Peripheral blood cells from 117 adult patients with anemia were classified according to iron status, and inflammatory activity, and the results of a hemoglobinopathy investigation as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β thalassemia (n = 25). The percentage of microcytic red cells, hypochromic red cells, and levels of hemoglobin content in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating between the different types of anemia. Results There was no significant difference between the iron deficient group and anemia of chronic disease associated with absolute iron deficiency in respect to any parameter. The percentage of hypochromic red cells was the best parameter to discriminate anemia of chronic disease with and without absolute iron deficiency (area under curve = 0.785; 95% confidence interval: 0.661–0.909, with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic red cells minus hypochromic red cells was very accurate in differentiating iron deficiency anemia and heterozygous β thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005; with sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8). Conclusion The indices related to red cells and reticulocytes have a moderate performance in identifying absolute iron deficiency in patients with anemia of chronic disease. PMID:25453653

  8. Anemia and end-stage renal disease in the developing world.

    PubMed

    Maïz, Hédi Ben; Abderrahim, Ezzeddine; Zouaghi, Karim

    2002-09-01

    In developing countries, multiple comorbidities such as malnutrition, parasitoses, and hemoglobinopathies contribute to the aggravation of anemia observed in patients with end-stage renal diseases. We analyze here the results of a retrospective evaluation of red-cells indices and iron parameters conducted at the end of December 2000 in 304 prevalent Tunisian patients (sex ratio, 1.05; mean age, 53.7 years) receiving chronic hemodialysis for a median duration of 49.6 months (range, 1.6 to 278). Anemia, observed in 87.8% of patients, was normochromic and normocytic in 73% of cases. Only 2% of patients had microcytic and hypochromic anemia. Iron deficiency was observed in 21.6% of anemic patients. The mean rate of hemoglobin was significantly higher in men and in patients with polycystic kidney disease as the cause of renal failure. There was a positive correlation between hemoglobin values and the quality of dialysis. Only 10.8% of patients were on recombinant human erythropoietin (rHuEPO) and 38% required regular transfusions. We conclude that anemia observed in our patients had, in most cases, the characteristics of renal anemia and could be attributed to a deficit of renal production of erythropoietin. However, for financial reasons, prescription of rHuEPO is rather restrictive and blood transfusion remains largely used. The nephrology community and dialysis providers should increase their efforts to improve the anemia care of dialyzed patients in developing countries.

  9. Excess copper chelating therapy for Wilson disease induces anemia and liver dysfunction.

    PubMed

    Harada, Masaru; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Shibata, Michihiko; Matsuhashi, Toru; Abe, Shintaro; Harada, Riko; Tabaru, Akinari

    2011-01-01

    A 37-year-old man was diagnosed with Wilson disease at the age of 14. His first manifestations were neurological. He was treated with trientine for more than 10 years and suffered from anemia and liver dysfunction. Wilson disease is a genetic disorder characterized by accumulation of copper in the body. Excess copper is toxic, but copper is an essential trace element. Copper-binding ceruloplasmin is important for iron metabolism. Excess copper chelating treatment-induced anemia and iron deposition in the liver was suspected. Proper monitoring of copper status is important for the management of Wilson disease.

  10. An investigation of the role of immunologic factors in anemia associated with canine heartworm disease.

    PubMed

    Werner, L L; Halliwell, R E; Jackson, R F; Needham, T C; Limpach, M

    1984-10-01

    Direct Coombs' antiglobulin tests were performed on 80 dogs with patent Dirofilaria immitis infection and 170 dogs negative for microfilaria of D. immitis. Presence or absence of anemia was determined by hematocrit in 55 of the heartworm negative dogs and 68 of the dogs with heartworm disease. Heartworm infected dogs showed a higher incidence (37%) of anemia than noninfected dogs (14.5%). Anemia was most prevalent in two groups of dogs with heartworm infection, one group showing vena caval syndrome (91%) and the other occult dirofilariasis (62.5%). These latter two groups of dogs also showed a significantly higher number of positive Coombs' reactions at 37 degrees C than other dogs with heartworm disease and the noninfected dogs. The number of positive Coombs' reactions at 4 degrees C among the total of 80 dogs with heartworm infection was significantly higher than that for dogs without heartworm disease. However, there was no positive correlation between anemia and the outcome of the Coombs' test at either temperature. These findings do not suggest that immunologic factors play a major role in the pathogenesis of anemia in dogs with heartworm disease.

  11. Management of iron deficiency anemia in inflammatory bowel disease - a practical approach.

    PubMed

    Stein, Jürgen; Dignass, Axel U

    2013-01-01

    Although anemia is the most common systemic manifestation of inflammatory bowel disease (IBD), among the broad spectrum of extraintestinal disease complications encountered in IBD, including arthritis and osteopathy, it has generally received little consideration. However, not only in terms of frequency, but also with regard to its potential effect on hospitalization rates and on the quality of life and work, anemia is indeed a significant and costly complication of IBD. Anemia is multifactorial in nature, the most prevalent etiological forms being iron deficiency anemia (IDA) and anemia of chronic disease. In a condition associated with inflammation, such as IBD, the determination of iron status using common biochemical parameters alone is inadequate. A more accurate assessment may be attained using new iron indices including reticulocyte hemoglobin content, percentage of hypochromic red cells or zinc protoporphyrin. While oral iron supplementation has traditionally been a mainstay of IDA treatment, it has also been linked to extensive gastrointestinal side effects and possible disease exacerbation. However, many physicians are still reluctant to administer iron intravenously, despite the wide availability of a variety of new IV preparations with improved safety profiles, and despite the recommendations of international expert guidelines. This article discusses improved diagnostic and therapeutic strategies based on new clinical insights into the regulation of iron homeostasis.

  12. [Hemolytic anemia as the first clinical presentation of Wilson disease: a pediatric case].

    PubMed

    Henao C, José A; Valverde Muñoz, Kathia; Ávila A, María L

    2016-12-01

    Wilson disease is an autosomal recessive disorder of the copper's hepatic metabolism; it results in toxicity due to accumulation of the mineral. The hemolytic anemia is present in 17% at some point of the disease, although it is a rare initial clinical presentation.

  13. Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease

    PubMed Central

    Li, Ya; Shi, Hao; Wang, Wei-Ming; Peng, Ai; Jiang, Geng-Ru; Zhang, Jin-Yuan; Ni, Zhao-Hui; He, Li-Qun; Niu, Jian-Ying; Wang, Nian-Song; Mei, Chang-Lin; Xu, Xu-Dong; Guo, Zhi-Yong; Yuan, Wei-Jie; Yan, Hai-Dong; Deng, Yue-Yi; Yu, Chen; Cen, Jun; Zhang, Yun; Chen, Nan

    2016-01-01

    Abstract This was the first multicenter, cross-sectional survey to assess the prevalence of anemia, patient awareness, and treatment status in China. Data of patients with chronic kidney disease (CKD; age, 18–75 years; both out- and inpatients) from 25 hospitals in Shanghai, seeking medical treatment at the nephrology department, were collected between July 1, 2012 and August 31, 2012. The prevalence, awareness, and treatment of anemia in patients with nondialysis CKD (ND-CKD) were assessed. Anemia was defined as serum hemoglobin (Hb) levels ≤12 g/dL in women and ≤13 g/dL in men. A total of 2420 patients with ND-CKD were included. Anemia was established in 1246 (51.5%) patients: 639 (51.3%) men and 607 (48.7%) women. The prevalence of anemia increased with advancing CKD stage (χ2trend = 675.14, P < 0.001). Anemia was more prevalent in patients with diabetic nephropathy (68.0%) than in patients with hypertensive renal damage (56.6%) or chronic glomerulonephritis (46.1%, both P < 0.001). Only 39.8% of the anemic patients received treatment with erythropoietin and 27.1% patients received iron products; furthermore, 22.7% of the patients started receiving treatment when their Hb level reached 7 g/dL. The target-achieving rate (Hb at 11–12 g/dL) was only 8.2%. Of the 1246 anemia patients, only 7.5% received more effective and recommended intravenous supplementation. Anemia is highly prevalent in patients with ND-CKD in China, with a low target-achieving rate and poor treatment patterns. The study highlights the need to improve multiple aspects of CKD management to delay the progression of renal failure. PMID:27310973

  14. Phagocytosis, oxidative burst, and produced reactive species are affected by iron deficiency anemia and anemia of chronic diseases in elderly.

    PubMed

    Paino, I M M; Miranda, J C; Marzocchi-Machado, C M; Cesarino, E J; de Castro, F A; de Souza, A M

    2009-01-01

    Iron and oxidative stress have a regulatory interplay. During the oxidative burst, phagocytic cells produce free radicals such as hypochlorous acid (HOCl). Nevertheless, scarce studies evaluated the effect of either iron deficiency anemia (IDA) or anemia of chronic disease (ACD) on phagocyte function in the elderly. The aim of the present study was to determine the oxidative burst, phagocytosis, and nitric oxide (*NO) and HOCl, reactive species produced by monocytes and neutrophils in elderly with ACD or IDA. Soluble transferrin receptor, serum ferritin, and soluble transferrin receptor/log ferritin (TfR-F) index determined the iron status. The study was constituted of 39 patients aged over 60 (28 women and 11 men) recruited from the Brazilian Public Health System. Oxidative burst fluorescence intensity per neutrophil in IDA group and HOCl generation in both ACD and IDA groups were found to be lower (p < 0.05). The percentages of neutrophils and monocytes expressing phagocytosis in ACD group were found to be higher (p < 0.05). There was an overproduction of *NO from monocytes, whereas the fundamental generation of HOCl appeared to be lower. Phagocytosis, oxidative burst, and *NO and HOCl production are involved in iron metabolism regulation in elderly patients with ACD and IDA.

  15. Health locus of control in patients with graves-basedow disease and hashimoto disease and their acceptance of illness.

    PubMed

    Basinska, Malgorzata Anna; Andruszkiewicz, Anna

    2012-01-01

    Adaptation to a chronic somatic disease depends on a variety of factors, including belief in health locus of control. Correlation between health locus of control and illness acceptance in patients with Graves-Basedow and Hashimoto diseases as well as correlation between health locus of control, illness acceptance, sex, and age. THREE METHODS WERE APPLIED: Multidimensional Health Locus of Control Scale by K.A. Wallston, B.S. Wallston and R. DeVellis; the Acceptance of Illness Scale by B.J. Felton, T.A. Revenson, and G.A. Hinrichsena; and a personal questionnaire. Two groups were subject to the research: 68 patients with Graves-Basedow disease and 54 patients with Hashimoto disease. Patients with Graves-Basedow disease, women above all, have their health locus of control in other persons (P = 0,001) and are less inclined to accept their illness (P = 0,005) when compared to patients with Hashimoto disease. A statistically significant correlation occurred between the age of patients and external (i.e., in other persons) health locus of control. Beliefs in health locus of control and type of illness in female patient group are predictors of illness acceptance (P = 0,0009).

  16. Approach to Anemia in Hospitalized Patients with Infectious Diseases; Is it Appropriate?

    PubMed

    Entezari-Maleki, Taher; Khalili, Hossein; Karimzadeh, Iman; Jafari, Sirous

    2015-01-01

    Anemia of chronic diseases (ACD) is a common problem in patients with infectious diseases and can influence the quality of life and patients' survival. Despite the clinical importance of ACD, data are still lacking regarding this problem in the infectious diseases. This study aimed to evaluate the prevalence, related factors, outcome and approaches to anemia in the infectious diseases ward. This retrospective study was performed to review the medical records of patients admitted to the infectious diseases department of Imam Khomeini hospital during a two-year period between 2009 and 2011. A standard protocol was developed to evaluate anemia. Patients' demographic data approaches to manage anemia and routine laboratory tests were recorded and compared with the protocol. Totally, 1,120 medical records were reviewed. ACD was recognized in 705 patients (63%). Only 5.1% of diagnostic and 8.7% of treatment approaches was based on the protocol. The majority of patients (89.4%) were received inappropriate treatment regarding. Mortality rate of patients with ACD was 3.4%. Moreover, a significant correlation between anemia and mortality was detected (r = 0.131; p = 0.026). A statistically significant correlation was also identified between patients' Hgb and ESR, CRP, reasons of admission, number of medications, and underlying diseases. In conclusion, results of this study suggested that ACD is a common problem in infectious diseases patients and significantly associated with patients' mortality. Moreover, the majority of studied patients were not received an appropriate diagnostic and treatment approach which arises more concerns regarding the management of ACD in infectious diseases setting.

  17. Heart failure with anemia: novel findings on the roles of renal disease, interleukins, and specific left ventricular remodeling processes.

    PubMed

    O'Meara, Eileen; Rouleau, Jean L; White, Michel; Roy, Karine; Blondeau, Lucie; Ducharme, Anique; Neagoe, Paul-Eduard; Sirois, Martin G; Lavoie, Joël; Racine, Normand; Liszkowski, Mark; Madore, François; Tardif, Jean-Claude; de Denus, Simon

    2014-09-01

    Anemia is a highly prevalent and strong independent prognostic marker in heart failure (HF), yet this association is not completely understood. Whether anemia is simply a marker of disease severity and concomitant chronic kidney disease or represents the activation of other detrimental pathways remains uncertain. We sought to determine which pathophysiological pathways are exacerbated in patients with HF, reduced ejection fraction (HFrEF) and anemia in comparison with those without anemia. In a prospective study involving 151 patients, selected biomarkers were analyzed, each representing proposed contributive mechanisms in the pathophysiology of anemia in HF. We compared clinical, echocardiographic, and circulating biomarkers profiles among patients with HFrEF and anemia (group 1), HFrEF without anemia (group 2), and chronic kidney disease with preserved EF, without established HF (chronic kidney disease control group 3). We demonstrate here that many processes other than those related to chronic kidney disease are involved in the anemia-HF relationship. These are linked to the pathophysiological mechanisms pertaining to left ventricular systolic dysfunction and remodeling, systemic inflammation and volume overload. We found that levels of interleukin-6 and interleukin-10, specific markers of cardiac remodeling (procollagen type III N-terminal peptide, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase 1, left atrial volume), myocardial stretch (NT-proBNP [N-terminal probrain natriuretic peptide]), and myocyte death (troponin T) are related to anemia in HFrEF. Anemia is strongly associated not only with markers of more advanced and active heart disease but also with the level of renal dysfunction in HFrEF. Increased myocardial remodeling, inflammation, and volume overload are the hallmarks of patients with anemia and HF. http://www.clinicaltrials.gov. Unique identifier: NCT00834691. © 2014 American Heart Association, Inc.

  18. Role of Hepcidin-25 in Chronic Kidney Disease: Anemia and Beyond.

    PubMed

    Ueda, Norishi; Takasawa, Kazuya

    2017-03-16

    Iron is an essential element for all living organisms, but produces toxic oxidants. Thus, iron homeostasis is tightly regulated in mammals. Hepcidin-25 (hepcidin) has emerged as a molecule that regulates iron metabolism. Binding of hepcidin to its receptor, ferroportin, inhibits intestinal iron absorption and iron efflux from hepatocytes and macrophages. Decreased hepcidin enhances iron absorption and efflux. Hepcidin could be predictive of iron status and the response to iron supplementation or erythropoietin-stimulating agents. Monitoring hepcidin is helpful for the management of anemia. Thus, it is urgent to obtain normal reference values in a large population of healthy subjects and to standardize various hepcidin assays, which enables to compare the data measured by different methods. Anemia is an important and common problem associated with chronic kidney disease (CKD), which is caused by erythropoietin deficiency, iron-restricted erythropoiesis, inflammation, hypoxia, vitamin D deficiency, hyperparathyroidism, and obesity. Anemia causes poor quality of life, progression of CKD, increased risk of cardiovascular events, and mortality. Besides its role for anemia, recent evidence suggests that hepcidin-25 plays a role in the pathogenesis and progression of kidney injury via modulation of iron-mediated oxidant injury. Despite accumulating experimental data, information about clinical significance of hepcidin-25 for anemia and kidney injury in CKD patients is scarce, especially in children. This review summarizes the current knowledge of a role of hepcidin-25 in the regulation of anemia and kidney injury in children and adults with CKD. Strategy for modulating hepcidin-25 to prevent anemia and kidney injury associated with CKD is also discussed.

  19. [Differential diagnosis of anemias].

    PubMed

    Szerafin, László; Jakó, János

    2005-02-13

    The authors describe the factors influencing of normal hemoglobin level, pathogenetic and morphological classification of anemias and the possibilities to distinguish their different types. They highlight features of iron deficiency anemia and anemia of chronic diseases. They summarise in tables the basis of laboratory diagnosis and possibility of identification of different types of anemias.

  20. Two cases of primary cold agglutinin disease associated with megaloblastic anemia.

    PubMed

    Imashuku, Shinsaku; Kudo, Naoko; Takagishi, Katsushige; Saigo, Katsuyasu

    2015-01-01

    We report two cases of primary cold agglutinin disease (CAD) associated with megaloblastic anemia in Japanese elderly patients. Case 1 was a 67-year-old male and Case 2 was a 55-year-old male. Both patients were diagnosed with primary CAD, with continuously high cold agglutinin titers (1 : >8,192 and 1 : 16,834, resp.), monoclonal IgM-kappa light chains, and no underlying disease. In addition, both patients had megaloblastic anemia due to vitamin B12 deficiency. One patient received rituximab and both received vitamin 12 supplementation. To date, no cooccurrence of primary CAD and megaloblastic anemia has been emphasized. Thus, the association of these hematological diseases may be incidental; however, given that CAD is an autoimmune disease which may show antibodies against intrinsic factor and gastric parietal cells, this association was thought to be probably not a coincidence. Clinicians should be aware of the possible simultaneous presence of autoimmune hemolytic/megaloblastic anemia in patients with primary CAD.

  1. Two Cases of Primary Cold Agglutinin Disease Associated with Megaloblastic Anemia

    PubMed Central

    Kudo, Naoko; Takagishi, Katsushige; Saigo, Katsuyasu

    2015-01-01

    We report two cases of primary cold agglutinin disease (CAD) associated with megaloblastic anemia in Japanese elderly patients. Case 1 was a 67-year-old male and Case 2 was a 55-year-old male. Both patients were diagnosed with primary CAD, with continuously high cold agglutinin titers (1 : >8,192 and 1 : 16,834, resp.), monoclonal IgM-kappa light chains, and no underlying disease. In addition, both patients had megaloblastic anemia due to vitamin B12 deficiency. One patient received rituximab and both received vitamin 12 supplementation. To date, no cooccurrence of primary CAD and megaloblastic anemia has been emphasized. Thus, the association of these hematological diseases may be incidental; however, given that CAD is an autoimmune disease which may show antibodies against intrinsic factor and gastric parietal cells, this association was thought to be probably not a coincidence. Clinicians should be aware of the possible simultaneous presence of autoimmune hemolytic/megaloblastic anemia in patients with primary CAD. PMID:25918651

  2. Postoperative Recurrence of Invasive Thymoma with Cold Agglutinin Disease and Autoimmune Hemolytic Anemia.

    PubMed

    Yoneda, Taro; Koba, Hayato; Tanimura, Kota; Ogawa, Naohiko; Watanabe, Satoshi; Hara, Johsuke; Abo, Miki; Sone, Takashi; Kimura, Hideharu; Kasahara, Kazuo

    A 50-year-old man presented to our hospital in 1995. Invasive thymoma was diagnosed and extended thymectomy and left upper lobe partial resection were performed. In 2013, he complained of dyspnea. Chest computed tomography showed postoperative recurrence of invasive thymoma. Several chemotherapies were administered. Severe anemia and an increase in the total bilirubin level were observed with chemotherapies. In additional, an examination showed that the direct Coombs test was positive. Cold agglutinin was also high. We herein experienced a rare case of postoperative recurrence of invasive thymoma with cold agglutinin disease and autoimmune hemolytic anemia.

  3. Bacillus cereus bacteremia and hemolytic anemia in a patient with hemoglobin SC disease.

    PubMed

    Rodgers, G M; Barrera, E; Martin, R R

    1980-08-01

    A patient with hemoglobin SC disease and cholelithiasis was found to have Bacillus cereus bacteremia. Hemolytic anemia developed, for which common causes of hemolysis were excluded, suggesting a relationship with the bacteremia. Following in vitro incubation, type O erythrocytes were hemolyzed by the culture, but not by a bacteria-free filtrate. This case confirms the association between sickle cell disorders and cholelithiasis with B cereus infections. In addition, it provides evidence for in vivo hemolysis with B cereus bacteremia, an organism not previously associated with hemolytic anemia.

  4. Red blood cell abnormalities and the pathogenesis of anemia in end-stage renal disease.

    PubMed

    Georgatzakou, Hara T; Antonelou, Marianna H; Papassideri, Issidora S; Kriebardis, Anastasios G

    2016-08-01

    Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in ESRD is controversial due to the "anemia paradox" phenomenon, which underlines the need for a more individualized approach to therapy. RBCs imprint the adverse effects of uremic, inflammatory, and oxidative stresses in a context of structural and functional deterioration that is associated with RBC removal signaling and morbidity risk. RBCs circulate in hostile plasma by raising elegant homeostatic defenses. Variability in primary defect, co-morbidity, and therapeutic approaches add complexity to the pathophysiological background of the anemic ESRD patient. Several blood components have been suggested as biomarkers of anemia-related morbidity and mortality risk in ESRD. However, a holistic view of blood cell and plasma modifications through integrated omics approaches and high-throughput studies might assist the development of new diagnostic tests and therapies that will target the underlying pathophysiologic processes of ESRD anemia.

  5. Simplification of an Erythropoiesis Model for Design of Anemia Management Protocols in End Stage Renal Disease

    PubMed Central

    Nichols, B; Shrestha, RP; Horowitz, J; Hollot, CV; Chait, Y; Germain, MJ; Gaweda, AE

    2014-01-01

    Many end stage renal disease (ESRD) patients suffer from anemia due to insufficient endogenous production of erythropoietin (EPO). The discovery of recombinant human EPO (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hgb) measurements. In order to facilitate the design of an AMP based on formal control design methods, we present a physiologically-relevant erythropoiesis model, and show that its nonlinear dynamics can be approximated using a static nonlinearity, a step that greatly simplifies AMP design. We demonstrate applicability of our results using clinical data. PMID:22254256

  6. Rheumatoid anemia.

    PubMed

    Masson, Charles

    2011-03-01

    Rheumatoid anemia is a typical example of anemia of chronic disease. It differs from other forms of anemia, such as iron deficiency anemia or iatrogenic anemia. Rheumatoid anemia is normochromic, normocytic or, less often, microcytic, aregenerative, and accompanied with thrombocytosis. Serum transferrin levels are normal or low, transferrin saturation is decreased, serum ferritin levels are normal or high, the soluble transferrin receptor (sTfR) is not increased (a distinguishing feature with iron deficiency anemia), and the sTfR/log ferritin ratio is lower than 1. This review discusses the prevalence and impact of rheumatoid anemia based on a review of the literature. Iron metabolism, absorption, diffusion, storage, and use by the bone marrow are described using published data on transferrin, ferritin, and hepcidin. Hepcidin is now recognized as a key factor in rheumatoid anemia, in conjunction with the cytokine interleukin-6 (IL-6). Hepcidin is a hormone that lowers serum iron levels and regulates iron transport across membranes, preventing iron from exiting the enterocytes, macrophages, and hepatocytes. In addition, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. The action of hepcidin is mediated by binding to the iron exporter ferroportin. Hepcidin expression in the liver is dependent on the protein hemojuvelin. Inflammation leads to increased hepcidin production via IL-6, whereas iron deficiency and factors associated with increased erythropoiesis (hypoxia, bleeding, hemolysis, dyserythropoiesis) suppress the production of hepcidin. Data from oncology studies and the effects of recombinant human IL-6 support a causal link between IL-6 production and the development of anemia in patients with chronic disease. IL-6 diminishes the proportion of nucleated erythroid cells in the bone marrow and lowers the serum iron level, and these abnormalities can be corrected by administering an IL-6 antagonist. IL-6 stimulates

  7. Methoxy polyethylene glycol-epoetin beta for anemia with chronic kidney disease.

    PubMed

    Ohashi, Naro; Sakao, Yukitoshi; Yasuda, Hideo; Kato, Akihiko; Fujigaki, Yoshihide

    2012-01-01

    Chronic kidney disease (CKD) is a risk factor for end-stage renal failure and cardiovascular events. In patients with CKD, anemia is often caused by decreased erythropoietin production relative to hemoglobin levels. As correction of anemia is associated with improved cardiac and renal function and quality of life, erythropoiesis-stimulating agents (ESAs) are standard therapy for anemia in CKD patients. However, traditional ESAs such as epoetin or darbepoetin have short half-lives and require frequent administration, dose changes, and close monitoring of hemoglobin concentration to maintain target hemoglobin levels. Methoxy polyethylene glycol-epoetin beta (MPG-EPO) is the only ESA that is generated by chemical modification of glycosylated erythropoietin through the integration of one specific, long, linear chain of polyethylene glycol. This ESA induces continuous erythropoietin receptor activation and has a long half-life (approximately 130 hours). Subcutaneous or intravenous administration of MPG-EPO once every 2 weeks or monthly achieved a high hemoglobin response rate in patients with anemia associated with CKD, regardless of whether the patient was undergoing dialysis. According to data from an observational time and motion study, MPG-EPO maintains hemoglobin levels when the same dose is administered, however infrequently. This suggests that compared with the use of traditional ESAs, administration of MPG-EPO reduces the overall time and cost associated with the management of anemia in CKD patients undergoing dialysis. MPG-EPO is generally well tolerated and most adverse events are of mild to moderate severity. The most commonly reported adverse effects are hypertension, nasopharyngitis, and diarrhea. Subcutaneous injection of MPG-EPO is significantly less painful than subcutaneous injection of darbepoetin. In conclusion, MPG-EPO is as effective and safe as traditional ESAs in managing renal anemia, irrespective of whether the patient is undergoing dialysis.

  8. Serum phosphorus and association with anemia among a large diverse population with and without chronic kidney disease

    PubMed Central

    Tran, Lac; Batech, Michael; Rhee, Connie M.; Streja, Elani; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J.; Sim, John J.

    2016-01-01

    Background We hypothesized that phosphorus has an effect on anemia in both normal kidney function and early chronic kidney disease (CKD). We sought to determine whether higher phosphorus levels are associated with anemia in a large diverse population without CKD and early CKD. Methods This study is a historical population-based study within the Kaiser Permanente Southern California health system (1 January 1998 to 31 December 2013) among individuals aged 18 years and older with estimated glomerular filtration rate >30 mL/min/1.73 m2 and measurements of serum phosphorus, creatinine and hemoglobin. Individuals were excluded if they had secondary causes of anemia. Odds ratio (OR) estimated for moderate anemia defined as hemoglobin <11 g/dL for both sexes. Mild anemia was defined as <12 g/dL (females) and <13 g/dL (males). Results Among 155 974 individuals, 4.1% had moderate anemia and 12.9% had mild anemia. Serum phosphorus levels ≥3.5 mg/dL were associated with both mild and moderate anemia. Moderate anemia OR (95% confidence interval) was 1.16 (1.04–1.29) for every 0.5 mg/dL phosphorus increase and 1.26 (1.07–1.48) in the highest versus middle phosphorus tertile. Additional independent anemia risk factors, including female sex, Asian race, diabetes, low albumin and low iron saturation, were observed, but did not alter the anemia–phosphorus association. Conclusions Higher phosphorus levels were associated with a greater likelihood for anemia in a population with early CKD and normal kidney function. Phosphorus may be a biomarker for anemia and may affect aspects of hematopoiesis. PMID:26254460

  9. Genetic overlap between Alzheimer’s disease and Parkinson’s disease at the MAPT locus

    PubMed Central

    Desikan, Rahul S.; Schork, Andrew J.; Wang, Yunpeng; Witoelar, Aree; Sharma, Manu; McEvoy, Linda K.; Holland, Dominic; Brewer, James B.; Chen, Chi-Hua; Thompson, Wesley K.; Harold, Denise; Williams, Julie; Owen, Michael J.; O’Donovan, Michael C.; Pericak-Vance, Margaret A.; Mayeux, Richard; Haines, Jonathan L.; Farrer, Lindsay A.; Schellenberg, Gerard D.; Heutink, Peter; Singleton, Andrew B.; Brice, Alexis; Wood, Nicolas W.; Hardy, John; Martinez, Maria; Choi, Seung Hoi; DeStefano, Anita; Ikram, M. Arfan; Bis, Joshua C.; Smith, Albert; Fitzpatrick, Annette L.; Launer, Lenore; van Duijn, Cornelia; Seshadri, Sudha; Ulstein, Ingun Dina; Aarsland, Dag; Fladby, Tormod; Djurovic, Srdjan; Hyman, Bradley T.; Snaedal, Jon; Stefansson, Hreinn; Stefansson, Kari; Gasser, Thomas; Andreassen, Ole A.; Dale, Anders M.

    2015-01-01

    We investigated genetic overlap between Alzheimer’s disease (AD) and Parkinson’s disease (PD). Using summary statistics (p-values) from large recent genomewide association studies (GWAS) (total n = 89,904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis p-value across 5 independent AD cohorts = 1.65 × 10−7). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD and extending prior work, we show that the MAPT region increases risk of Alzheimer’s neurodegeneration. PMID:25687773

  10. Five-Year Status of Malaria (a Disease Causing Anemia) in Yazd, 2008-2012.

    PubMed

    Fattahi Bafghi, A; Pourmazar, S A; Shamsi, F

    2013-01-01

    Yazd province which is the host of local and foreign immigrants may be faced with contacting malaria. Plasmodium falciparum malaria remains a major cause of mortality throughout in the tropical regions of the world. Pthophysiologic mechanisms of anemia in malaria is such as direct invasion of Red cells, anemia of chronic disease hypersplenism, Hemophagocytic syndrome and erythrophagocytosis, dyserythropoirsis, immune haemolysis and cytokine deregulation anemia of chronic disorder is characterized by moderate to mild normocytic, normochromic anemia along with microcytic hypochromic cells. Malaria occurs predominantly in children in the first three years of life. The purpose of this study was Demographic study of malaria during 2008 to 2012 in Yazd. This study was an analytic-descriptive and manner descriptive study. All episodes (Imported Malaria) of disease from 2008 to 2012 which were documented in Yazd Central Health Service were carefully studied and reported. A total of 206 confirmed reported malaria patients from 2008 to 2012 were studied; Plasmodium (P). vivax species was mostly, 187(90.78%) and Plasmodium (P). Malaria species was Lesley, 1(0.49%). The mean age groups, accommodation with local malaria and years of reported outbreaks of different strains of the parasite conducted by Fisher exact Test, showed no significant difference(P-value>0.05), but the mean of foreigner immigrants of outbreaks of different strains of the parasite conducted by Fisher exact Test, showed significant difference (P-value= 0.01). Although malaria has been designed on elimination program in Iran, but in the province of Yazd is reported imported malaria and its importance in causing anemia and other blood disorders is not negligible.

  11. [Hronic heart failure and concomitant diseases in elderly patients: anemia and cardio-renal anemic syndrome].

    PubMed

    Larina, V N; Bart, B Ia; Raspopova, T N; Larin, V G

    2014-01-01

    to assess impact of anemia on chronic heart failure (CHF) course in elderly patients in primary care setting. Methods. We examined 164 outpatients (n=164) aged 60-85 years with clinically stable CHF due to ischemic heart disease and arterial hypertension. All patients underwent clinical, laboratorial evaluation, ECG, EchoCG measurements, 6 min walk test. Patients were categorized according to the presence of anemia, as defined by the WHO criteria (hemoglobin levels <13 g/dl in men and <12 g/dl in women). Median duration of follow up was 1.85 (1.0-4.75) years. Results. Anemia was found in 32.9%, cardio-renal anemic syndrome (CRAS) in 23.2% of patients. In all patients anemia was mild (Hb>9 g/dl). It was associated with diabetes mellitus (odds ratio [R] 2.2, 95% CI 1.03-4.69, =0.041), high creatinine level (R 2.76, 95% CI 1.25-6.12, =0.012) and chronic kidney disease (R 5.66, 95% CI 2.51-12.77, <0.001). During follow-up mortality rate was similar among anemic and non-anemic patients (27.8 vs 30%, =0.768). Patients with CRAS had worse survival compared with patients of the same age without anemia and preserved kidney function (=0.004). Age >75 years (R 3.58, 95% CI 1.59-7.99, =0.002), diabetes (R 2.68, 95% CI 1.19-6.04, =0.018), history of myocardial infarction (R 2.7, 95% CI 1.24-6.04, =0.013), systolic blood pressure <110 mm Hg (OR 2.49, 95% CI 1.09-5.71, =0.030), complete left bundle branch block (LBBB) (OR 2.79, 95% CI 1.26-8.22, =0.012), creatinine >130 mmol/l (OR 3.53, 95% CI 1.51-8.22, =0.004) were predictors of mortality of elderly patients with CRAS. Conclusions. CHF patients with and without anemia had similar survival but survival of those with CRAS was worse compared with patients without anemia and preserved kidney function. Age >75 years, diabetes mellitus, history of myocardial infarction, low systolic blood pressure, complete LBBB, high creatinine level were predictors of mortality in patients with CRAS.

  12. Functional analysis of the TRIB1 associated locus linked to plasma triglycerides and coronary artery disease.

    PubMed

    Douvris, Adrianna; Soubeyrand, Sébastien; Naing, Thet; Martinuk, Amy; Nikpay, Majid; Williams, Andrew; Buick, Julie; Yauk, Carole; McPherson, Ruth

    2014-06-03

    The TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease in humans. The lipid-associated single nucleotide polymorphisms (SNPs), identified by genome-wide association studies, are located ≈30 kb downstream from TRIB1, suggesting complex regulatory effects on genes or pathways relevant to hepatic triglyceride metabolism. The goal of this study was to investigate the functional relationship between common SNPs at the TRIB1 locus and plasma lipid traits. Characterization of the risk locus reveals that it encompasses a gene, TRIB1-associated locus (TRIBAL), composed of a well-conserved promoter region and an alternatively spliced transcript. Bioinformatic analysis and resequencing identified a single SNP, rs2001844, within the promoter region that associates with increased plasma triglycerides and reduced high-density lipoprotein cholesterol and coronary artery disease risk. Further, correction for triglycerides as a covariate indicated that the genome-wide association studies association is largely dependent on triglycerides. In addition, we show that rs2001844 is an expression trait locus (eQTL) for TRIB1 expression in blood and alters TRIBAL promoter activity in a reporter assay model. The TRIBAL transcript has features typical of long noncoding RNAs, including poor sequence conservation. Modulation of TRIBAL expression had limited impact on either TRIB1 or lipid regulatory genes mRNA levels in human hepatocyte models. In contrast, TRIB1 knockdown markedly increased TRIBAL expression in HepG2 cells and primary human hepatocytes. These studies demonstrate an interplay between a novel locus, TRIBAL, and TRIB1. TRIBAL is located in the genome-wide association studies identified risk locus, responds to altered expression of TRIB1, harbors a risk SNP that is an eQTL for TRIB1 expression, and associates with plasma triglyceride concentrations. © 2014 The Authors. Published on behalf of the

  13. The APOE locus advances disease progression in late onset familial Alzheimer`s disease but is not causative

    SciTech Connect

    Crawford, F.; Bennett, C.; Osborne, A.

    1994-09-01

    An association has been observed in several independent data sets between late onset Alzheimer`s disease (AD) and the APOE locus on chromosomes 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the {epsilon}4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and nonstringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease-free survival suggested that APOE genotype contributes a small fraction of the total variance, indicating that the APOE locus is a poor predictor of disease-free survival time within late onset families. We suggest that the APOE locus enhances the rate of progression of the disease in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause this disease.

  14. The Global Burden of Anemia.

    PubMed

    Kassebaum, Nicholas J

    2016-04-01

    Anemia is an important cause of health loss. We estimated levels and trends of nonfatal anemia burden for 23 distinct etiologies in 188 countries, 20 age groups, and both sexes from 1990 to 2013. All available population-level anemia data were collected and standardized. We estimated mean hemoglobin, prevalence of anemia by severity, quantitative disability owing to anemia, and underlying etiology for each population using the approach of the Global Burden of Disease, Injuries and Risk Factors 2013 Study. Anemia burden is high. Developing countries account for 89% of all anemia-related disability. Iron-deficiency anemia remains the dominant cause of anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A rare association of celiac disease and aplastic anemia: case report of a child and review of literature.

    PubMed

    Badyal, Rama Kumari; Sachdeva, Man Updesh Singh; Varma, Neelam; Thapa, Babu Ram

    2014-01-01

    An association between severe aplastic anemia and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus, and thyroid disorders. Herein we report a patient with celiac disease who was not strictly following a gluten-free diet and presented with progressive pallor, fever, and weakness of 1 month's duration. On investigation, he had pancytopenia, which on subsequent evaluation revealed aplastic anemia. An association between aplastic anemia and celiac disease has rarely been reported. To the best of author's knowledge, only 1 pediatric case of celiac disease associated with aplastic anemia has been published. This is the second report to suggest such an association in children.

  16. Dental Perspective of Rare Disease of Fanconi Anemia: Case Report with Review

    PubMed Central

    Goswami, Mridula; Bhushan, Urvashi; Goswami, Manoj

    2016-01-01

    Fanconi anemia is an extremely rare genetic disease characterized by chromosomal instability that induces congenital alterations in individuals. It causes defective hemopoiesis ultimately leading to bone marrow failure. Patients are susceptible to recurrent infections and increased risk of hemorrhage, as well as delayed and poor wound healing. Herein, we report a case of Fanconi anemia in which various classical signs of the disease were present. The patient has been on regular follow-up since three and a half years for management of dental problems. The different aspects of this rare disorder are discussed with emphasis on oral manifestations and their influence on the general health of affected patients. Due to an increased susceptibility to developing cancers in this specific population, it is imperative for pediatric dentists to know about the common oral manifestations and potentially cancerous lesions, in order to make an early diagnosis and provide comprehensive care and maintenance of oral health in affected individuals. PMID:27013901

  17. Anti-M Antibody Induced Prolonged Anemia Following Hemolytic Disease of the Newborn Due to Erythropoietic Suppression in 2 Siblings.

    PubMed

    Ishida, Atsushi; Ohto, Hitoshi; Yasuda, Hiroyasu; Negishi, Yutaka; Tsuiki, Hideki; Arakawa, Takeshi; Yagi, Yoshihito; Uchimura, Daisuke; Miyazaki, Toru; Ohashi, Wataru; Takamoto, Shigeru

    2015-08-01

    Hemolytic disease of the newborn (HDN) arising from MNSs incompatibility is rare, with few reports of prolonged anemia and reticulocytopenia following HDN. We report the younger of 2 male siblings, both of whom had anti-M-induced HDN and anemia persisting for over a month. Peripheral reticulocytes remained inappropriately low for the degree of anemia, and they needed multiple red cell transfusions. Viral infections were ruled out. Corticosteroids were given for suspected pure red cell aplasia. Anemia and reticulocytopenia subsequently improved. Colony-forming unit erythroid assay revealed erythropoietic suppression of M antigen-positive erythroid precursor cells cultured with maternal or infant sera containing anti-M. In conclusion, maternal anti-M caused HDN and prolonged anemia by erythropoietic suppression in 2 siblings.

  18. Lafora disease is not linked to the Unverricht-Lundborg locus.

    PubMed

    Labauge, P; Beck, C; Bellet, H; Coquillat, G; Vespignani, H; Dulac, O; Gilgenkrantz, S; Dravet, C; Genton, P; Pellissier, J F

    1995-02-27

    Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis.

  19. Serodiagnosis of celiac disease in children referred for evaluation of anemia: a pediatric hematology unit's experience.

    PubMed

    Bansal, Deepak; Trehan, Amita; Gupta, Mukesh Kumar; Varma, Neelam; Marwaha, R K

    2011-01-01

    Children presenting with typical clinical features of celiac disease (CD) are diagnosed relatively easily, however, diagnosis remains challenging and is often delayed when they present with 'difficult to treat anemia' without overt gastrointestinal manifestations. Index study was undertaken to report profile of patients referred to pediatric hematology unit with 'difficult anemia' who subsequently were diagnosed with CD. The records of 83 patients (1988-2008) with CD were scrutinized retrospectively who had presented with predominant hematological manifestations. CD was confirmed histologically in 31 (37%), while 52 (63%) were diagnosed by serology alone. The mean age at diagnosis was 8.0 ± 2.8 years. The mean duration of symptom-diagnosis interval was 40.9 ± 30.6 months. Eighty-one (98%) children had anemia (Hb < 11 g/dl) and 55 (66%) had received iron supplements without discernible benefit. Thirty-nine (47%) patients received a blood transfusion. Thirty-six (43%) patients did not have diarrhea. Majority of the patients had either a microcytic-hypochromic (48%) or dimorphic (43%) anemia. Twenty-four (33%) had thrombocytosis, while 5 (7%) had thrombocytopenia. Mean duration of follow-up for patients on roll in the clinic for more than six months was 17.7 ± 20.9 months. Pediatricians and hematologists need to be aware of the extra-intestinal manifestations of CD. Prolonged duration of symptoms and a diagnosis at a relatively older age is striking in children presenting with predominantly hematological manifestations. Investigations for CD are recommended in children presenting with iron deficiency anemia refractory to hematinics or who have coexisting growth retardation. Necessity for biopsy in overtly symptomatic cases is discussed.

  20. The Cost-Effectiveness of Anemia Treatment for Persons with Chronic Kidney Disease

    PubMed Central

    Yarnoff, Benjamin O.; Hoerger, Thomas J.; Simpson, Siobhan A.; Pavkov, Meda E.; Burrows, Nilka R.; Shrestha, Sundar S.; Williams, Desmond E.; Zhuo, Xiaohui

    2016-01-01

    Background Although major guidelines uniformly recommend iron supplementation and erythropoietin stimulating agents (ESAs) for managing chronic anemia in persons with chronic kidney disease (CKD), there are differences in the recommended hemoglobin (Hb) treatment target and no guidelines consider the costs or cost-effectiveness of treatment. In this study, we explored the most cost-effective Hb target for anemia treatment in persons with CKD stages 3–4. Methods and Findings The CKD Health Policy Model was populated with a synthetic cohort of persons over age 30 with prevalent CKD stages 3–4 (i.e., not on dialysis) and anemia created from the 1999–2010 National Health and Nutrition Examination Survey. Incremental cost-effectiveness ratios (ICERs), computed as incremental cost divided by incremental quality adjusted life years (QALYs), were assessed for Hb targets of 10 g/dl to 13 g/dl at 0.5 g/dl increments. Targeting a Hb of 10 g/dl resulted in an ICER of $32,111 compared with no treatment and targeting a Hb of 10.5 g/dl resulted in an ICER of $32,475 compared with a Hb target of 10 g/dl. QALYs increased to 4.63 for a Hb target of 10 g/dl and to 4.75 for a target of 10.5 g/dl or 11 g/dl. Any treatment target above 11 g/dl increased medical costs and decreased QALYs. Conclusions In persons over age 30 with CKD stages 3–4, anemia treatment is most cost-effective when targeting a Hb level of 10.5 g/dl. This study provides important information for framing guidelines related to treatment of anemia in persons with CKD. PMID:27404556

  1. Circulating thrombopoietin levels in normal healthy blood donors and in aplastic anemia patients in relation to disease severity

    PubMed Central

    Singh, Abhay; Verma, Anupam; Nityanand, Soniya; Chaudhary, Rajendra; Elhence, Priti

    2015-01-01

    Background: Thrombopoietin (TPO) is the key hematopoietic growth factor regulating the production of platelets from bone marrow megakaryocytes and maintaining platelet hemostasis. This study was done to find any relationship between the levels of thrombopoietin and the severity of disease in patients with aplastic anemia. Materials and Methods: Serum samples were collected from 52 patients with a confirmed diagnosis of aplastic anemia and 45 normal healthy blood donors of both sexes over a period of 2 years, and TPO was estimated by using commercially available TPO-specific-enzyme-linked immunosorbent assay. Results: The median TPO level of 1190 pg/ml (range 625-7651 pg/ml) in aplastic anemia patients was significantly higher than the median TPO level of 121.1 pg/ml (81.25-237.7 pg/ml) in normal healthy blood donors (P = 0.000). No significant difference was observed in TPO levels of male and female patients (P = 0.453). The median TPO concentrations observed in very severe aplastic anemia, severe aplastic anemia, and nonsevere aplastic anemia were 2765 pg/ml (range 625-6451 pg/ml), 1190 pg/ml (range 672.1-7651 pg/ml), and 1111.5 pg/ml (range 761.1-2289.2 pg/ml), respectively. TPO in patients of very severe aplastic anemia was significantly higher than patients of nonsevere aplastic anemia (P = 0.043), with no significant relation among rest of the groups. Discussion: TPO levels in aplastic anemia patients were significantly higher than in healthy blood donors; however, in aplastic anemia patients TPO levels were significantly higher only in patients with very severe disease. PMID:25722577

  2. Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

    PubMed Central

    Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

    2012-01-01

    Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

  3. Newly Diagnosed Anemia Increases Risk of Parkinson's disease: A Population-Based Cohort Study.

    PubMed

    Hong, Chien Tai; Huang, Yao Hsien; Liu, Hung Yi; Chiou, Hung-Yi; Chan, Lung; Chien, Li-Nien

    2016-07-14

    Anemia and low hemoglobin have been identified to increase Parkinson's disease (PD) risk. This population-based cohort study investigated PD risk in newly diagnosed anemic patients by using data from the Taiwan National Health Insurance Research Database. All newly diagnosed anemic patients (n = 86,334) without a history of stroke, neurodegenerative diseases, traumatic brain injury, major operations, or blood loss diseases were enrolled. A cohort of nonanemic controls, 1:1 matched with anemic patients on the basis of the demographics and pre-existing medical conditions, was also included. Competing risk analysis was used to evaluate PD risk in anemic patients compared with that in their matched controls. The adjusted hazard ratio (aHR) of PD risk in the anemic patients was 1.36 (95% confidence interval [CI]: 1.22-1.52, p < 0.001). Iron deficiency anemia (IDA) patients tended to exhibit a higher PD risk (aHR: 1.49; 95% CI: 1.24-1.79, p < 0.001). Furthermore, Iron supplement did not significantly affect the PD risk: the aHRs for PD risk were 1.32 (95% CI: 1.07-1.63, p < 0.01) and 1.86 (95% CI: 1.46-2.35, p < 0.001) in IDA patients with and without iron supplementation, respectively. The population-based cohort study indicated newly diagnosed anemia increases PD risk.

  4. Analysis of non-typeable Haemophilus influenzae in invasive disease reveals lack of the capsule locus.

    PubMed

    Lâm, T-T; Claus, H; Frosch, M; Vogel, U

    2016-01-01

    Among invasive Haemophilus influenzae, unencapsulated strains have largely surpassed the previously predominant serotype b (Hib) because of Hib vaccination. Isolates without the genomic capsule (cap) locus are designated non-typeable H. influenzae (NTHi). They are different from capsule-deficient variants that show deletion of the capsule transport gene bexA within the cap locus. The frequency of capsule-deficient variants in invasive disease is unknown. We analysed 783 unencapsulated invasive isolates collected over 5 years in Germany and found no single capsule-deficient isolate. Invasive unencapsulated strains in Germany were exclusively NTHi. A negative serotyping result by slide agglutination was therefore highly predictive for NTHi.

  5. Characterization of the anemia of inflammatory disease in cats with abscesses, pyothorax, or fat necrosis.

    PubMed

    Ottenjann, Mareike; Weingart, Christiane; Arndt, Gisela; Kohn, Barbara

    2006-01-01

    The purpose of this study was to describe the anemia of inflammatory disease (AID) in cats with naturally-occurring inflammatory diseases, such as abscesses (n = 12), pyothorax (n = 6), and fat necrosis (n = 3). Exclusion criteria were positive FeLV/FIV tests, neoplasia, nephro-, hepato- or endocrinopathies, and blood loss anemia. CBC, clinical biochemistry, measurements of serum erythropoietin, iron, total iron-binding capacity (TIBC), ferritin, acute phase proteins, erythrocytic osmotic fragility (OF), and Coombs' tests were performed. A decrease in hematocrit of 1-28% (median, 10%) occurred within 3-16 days (median, 8 days). The anemia was mild (n = 11), moderate (n = 8), or severe (n = 2). In most cases it was normocytic normochromic, non-regenerative (n = 18), or mildly regenerative (n = 3). Sixteen cats had leukocytosis and 5 mild hyperbilirubinemia. The Coombs' test results were negative for 8 cats and positive for 1 cat. OF was increased in 2 out of 14 cats. Hypoalbuminemia (n = 18) and hyperglobulinemia (n = 16) resulted in a lowered albumin/globulin-ratio in 19 cats. Iron and TIBC were low in 2/19 and 6 /19 cats, respectively. The ferritin concentrations were normal in 7 cats and increased in 12 cats. The acute phase proteins alpha1-acid-glycoprotein and haptoglobin were increased in 14/14 and 13/14 cats, respectively. Erythropoietin was normal (n = 4), mildly increased (n = 7) or severely increased (1). Two cats were euthanized due to their underlying disease, 3 cats needed blood transfusions. AID in cats is usually mild to moderate, non-regenerative, and normocytic normochromic. It can be clinically relevant causing severe and transfusion-dependent anemia. AID seems to be multifactorial with evidence of iron sequestration, decreased RBC survival, and insufficient erythropoietin production and bone marrow response. Specific and supportive therapy, including transfusions, can reverse these processes.

  6. COEXISTENCE OF ADDISON'S DISEASE AND PERNICIOUS ANEMIA: IS THE NEW CLASSIFICATION OF AUTOIMMUNE POLYGLANDULAR SYNDROME APPROPRIATE?

    PubMed

    Vrkljan, Ana Marija; Pašalić, Ante; Strinović, Mateja; Perić, Božidar; Kruljac, Ivan; Miroševć, Gorana

    2015-06-01

    A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man was admitted due to fatigue, malaise and inappetence. He had a history of primary hypothyroidism and was on levothyroxine substitution therapy. One year before, he was diagnosed with normocytic anemia and vitamin B12 deficiency, which was treated with vitamin B12 substitution therapy. Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the diagnosis of Addison's disease was established. Additional laboratory workup showed positive parietal cell antibodies. However, his vitamin B12 levels were increased due to vitamin B12 supplementation therapy, which was initiated earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell antibodies and atrophic gastritis, the patient was diagnosed with pernicious anemia. Hydrocortisone supplementation therapy was administered and titrated according to urinary-free cortisol levels. Electrolyte disbalance and red blood cell count were normalized. This case report demonstrates rather unique features of pernicious anemia in a patient with Addison's disease. It also highlights the link between type II and type III APS. Not only do they share the same etiological factors, but also overlap in pathophysiological and clinical characteristics. This case report favors older classification of APS, which consolidates all endocrine and other organ-specific autoimmune diseases into one category. This is important since it might help avoid pitfalls in the diagnosis and treatment of patients with APS.

  7. Epidemiology and treatment of relative anemia in children with sickle cell disease in sub-Saharan Africa.

    PubMed

    Bello-Manga, Halima; DeBaun, Michael R; Kassim, Adetola A

    2016-11-01

    Sickle cell disease (SCD) is the most common inherited hemoglobinopathy in the world, with the majority of cases in sub-Saharan Africa. Concomitant nutritional deficiencies, infections or exposure to environmental toxins exacerbate chronic anemia in children with SCD. The resulting relative anemia is associated with increased risk of strokes, poor cognitive function and impaired growth. It may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa. This review will focus on the epidemiology, clinical sequelae, and treatment of relative anemia in children with SCD living in low and middle-income countries in sub-Saharan Africa. Areas covered: The causes and treatment of relative anemia in children with SCD in sub-Saharan Africa. The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles regarding relative anemia in children with SCD in sub-Saharan Africa. Expert commentary: Anemia due to nutritional deficiencies and infectious diseases such as helminthiasis and malaria are prevalent in sub-Saharan Africa. Their co-existence in children with SCD increases morbidity and mortality. Therefore, preventing, diagnosing and treating the underlying cause of this relative anemia will improve SCD-related outcomes in children in sub-Saharan Africa.

  8. Locus-Specific Mutation Databases for Neurodegenerative Brain Diseases

    PubMed Central

    Cruts, Marc; Theuns, Jessie; Van Broeckhoven, Christine

    2012-01-01

    The Alzheimer disease and frontotemporal dementia (AD&FTLD) and Parkinson disease (PD) Mutation Databases make available curated information of sequence variations in genes causing Mendelian forms of the most common neurodegenerative brain disease AD, frontotemporal lobar degeneration (FTLD), and PD. They are established resources for clinical geneticists, neurologists, and researchers in need of comprehensive, referenced genetic, epidemiologic, clinical, neuropathological, and/or cell biological information of specific gene mutations in these diseases. In addition, the aggregate analysis of all information available in the databases provides unique opportunities to extract mutation characteristics and genotype–phenotype correlations, which would be otherwise unnoticed and unexplored. Such analyses revealed that 61.4% of mutations are private to one single family, while only 5.7% of mutations occur in 10 or more families. The five mutations with most frequent independent observations occur in 21% of AD, 43% of FTLD, and 48% of PD families recorded in the Mutation Databases, respectively. Although these figures are inevitably biased by a publishing policy favoring novel mutations, they probably also reflect the occurrence of multiple rare and few relatively common mutations in the inherited forms of these diseases. Finally, with the exception of the PD genes PARK2 and PINK1, all other genes are associated with more than one clinical diagnosis or characteristics thereof. Hum Mutat 33:1340–1344, 2012. © 2012 Wiley Periodicals, Inc. PMID:22581678

  9. Anemia in pregnancy.

    PubMed

    Horowitz, Kari M; Ingardia, Charles J; Borgida, Adam F

    2013-06-01

    Hemodynamic changes occur in pregnancy to prepare for expected blood loss at delivery. Physiologic anemia occurs in pregnancy because plasma volume increases more quickly than red cell mass. Anemia is most commonly classified as microcytic, normocytic, or macrocytic. Iron deficiency anemia accounts for 75% of all anemias in pregnancy. Oral iron supplementation is the recommended treatment of iron deficiency anemia in pregnancy. Parenteral iron and erythropoietin can also be used in severe or refractory cases. Outcomes and treatments for other forms of inherited and acquired anemias in pregnancy vary by disease, and include nutritional supplementation, corticosteroids, supportive transfusions, and splenectomy.

  10. Anemia in older persons.

    PubMed

    Bross, Michael H; Soch, Kathleen; Smith-Knuppel, Teresa

    2010-09-01

    Anemia in older persons is commonly overlooked despite mounting evidence that low hemoglobin levels are a significant marker of physiologic decline. Using the World Health Organization definition of anemia (hemoglobin level less than 13 g per dL [130 g per L] in men and less than 12 g per dL [120 g per L] in women), more than 10 percent of persons older than 65 years are anemic. The prevalence increases with age, approaching 50 percent in chronically ill patients living in nursing homes. There is increasing evidence that even mild anemia is associated with increased morbidity and mortality. Anemia warrants evaluation in all older persons, except those at the end of life or who decline interventions. About one third of persons have anemia secondary to a nutritional deficiency, one third have anemia caused by chronic inflammation or chronic kidney disease, and one third have unexplained anemia. Nutritional anemia is effectively treated with vitamin or iron replacement. Iron deficiency anemia often is caused by gastrointestinal bleeding and requires further investigation in most patients. Anemia of chronic inflammation or chronic kidney disease may respond to treatment of the underlying disease and selective use of erythropoiesis-stimulating agents. The treatment of unexplained anemia is difficult, and there is little evidence that treatment decreases morbidity and mortality, or improves quality of life. Occasionally, anemia may be caused by less common but potentially treatable conditions, such as autoimmune hemolytic anemia, malignancy, or myelodysplastic syndrome.

  11. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.

    PubMed

    Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B; Lee, Yi-Ching; Shimizu, Chisato; Wright, Victoria J; Yeung, Rae S M; Tan, Dennis E K; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu-Fai; Huang, Guo-Ying; Yang, Wanling; Park, In-Sook; Lee, Jong-Keuk; Wu, Jer-Yuarn; Levin, Michael; Burns, Jane C; Burgner, David; Kuijpers, Taco W; Hibberd, Martin L

    2011-11-13

    Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

  12. Estimating locus heterogeneity in autosomal dominant polycystic kidney disease (ADPKD) in the Spanish population.

    PubMed Central

    Peral, B; San Millán, J L; Hernández, C; Valero, A; Lathrop, G M; Beckmann, J S; Moreno, F

    1993-01-01

    Although most mutations causing ADPKD in European populations have been mapped to the PKD1 locus on chromosome 16, some of them appear to be unlinked to this locus. To evaluate the incidence of unlinked mutations in Spain we have typed 31 Spanish families from different geographical sites for six closely linked DNA polymorphic marker loci flanking PKD1 detected by probes D16S85, D16S21, D16S259, D16S125, D16S246, and D16S80. Multilocus linkage analysis indicated that in 26 families the disease resulted from PKD1 mutations, whereas in three families it resulted from mutations in a locus other than PKD1. The two other families were not informative. Using the HOMOG test, the incidence of the PKD1 linked mutations in Spain is 85%. Multipoint linkage analysis in the 26 PKD1 families showed that the disease locus lies in the interval between D16S259(pGGG1) and D16S125(26.6). PMID:7905535

  13. The Huntington disease locus is most likely within 325 kilobases of the chromosome 4p telomere

    SciTech Connect

    Doggett, N.A.; Cheng, J.F.; Smith, C.L.; Cantor, C.R. )

    1989-12-01

    The genetic defect responsible for Huntington disease was originally localized near the tip of the short arm of chromosome 4 by genetic linkage to the locus D4S10. Several markers closer to Huntington disease have since been isolated, but these all appear to be proximal to the defect. A physical map that extends from the most distal of these loci, D4S90, to the telomere of chromosome 4 was constructed. This map identifies at least two CpG islands as markers for Huntington disease candidate genes and places the most likely location of the Huntington disease defect remarkably close (within 325 kilobases) to the telomere.

  14. The Alzheimer disease BIN1 locus as a modifier of GBA-associated Parkinson disease.

    PubMed

    Gan-Or, Z; Amshalom, I; Bar-Shira, A; Gana-Weisz, M; Mirelman, A; Marder, K; Bressman, S; Giladi, N; Orr-Urtreger, A

    2015-11-01

    GBA mutations are among the most common genetic risk factors for Parkinson disease (PD) worldwide. We aimed to identify genetic modifiers of the age at onset (AAO) in GBA-associated PD. The study included a genome-wide discovery phase, including a cohort of 79 patients with the GBA p.N370S mutation, and candidate validation and replication analyses of 8 SNPs in patients with mild (n = 113) and severe (n = 41) GBA mutations. Genotyping was performed using the Affymetrix human SNP 6.0 array and TaqMan assays. In the genome-wide phase, none of the SNPs passed the genome-wide significance threshold. Eight SNPs were selected for further analysis from the top hits. In all GBA-associated PD patients (n = 153), the BIN1 rs13403026 minor allele was associated with an older AAO (12.4 ± 5.9 years later, p = 0.0001), compared to patients homozygous for the major allele. Furthermore, the AAO was 10.7 ± 6.8 years later in patients with mild GBA mutations, (p = 0.005, validation group), and 17.1 ± 2.5 years later in patients with severe GBA mutations (p = 0.01, replication). Our results suggest that alterations in the BIN1 locus, previously associated with Alzheimer disease, may modify the AAO of GBA-associated PD. More studies in other populations are required to examine the role of BIN1-related variants in GBA-associated PD.

  15. Tomato mutants altered in bacterial disease resistance provide evidence for a new locus controlling pathogen recognition.

    PubMed Central

    Salmeron, J M; Barker, S J; Carland, F M; Mehta, A Y; Staskawicz, B J

    1994-01-01

    We have employed a genetic approach to study the resistance of tomato to the phytopathogenic bacterium Pseudomonas syringae pv tomato. Resistance to P. s. tomato depends upon expression of the Pto locus in tomato, which encodes a protein with similarity to serine/threonine protein kinases and recognizes pathogen strains expressing the avirulence gene avrPto. Eleven tomato mutants were isolated with altered resistance to P. s. tomato strains expressing avrPto. We identified mutations both in the Pto resistance locus and in a new locus designated Prf (for Pseudomonas resistance and fenthion sensitivity). The genetic approach allowed us to dissect the roles of these loci in signal transduction in response to pathogen attack. Lines carrying mutations in the Pto locus vary 200-fold in the degree to which they are susceptible to P. s. tomato strains expressing avrPto. The pto mutants retain sensitivity to the organophosphate insecticide fenthion; this trait segregates with Pto in genetic crosses. This result suggested that contrary to previous hypotheses, the Pto locus controls pathogen recognition but not fenthion sensitivity. Interestingly, mutations in the prf locus result in both complete susceptibility to P. s. tomato and insensitivity to fenthion, suggesting that Prf plays a role in tomato signaling in response to both pathogen elicitors and fenthion. Because pto and prf mutations do not alter recognition of Xanthomonas campestris strains expressing avrBsP, an avirulence gene recognized by all tested tomato cultivars, Prf does not play a general role in disease resistance but possibly functions specifically in resistance against P. s. tomato. Genetic analysis of F2 populations from crosses of pto and prf homozygotes indicated that the Pto and Prf loci are tightly linked. PMID:7911348

  16. Anemia (For Parents)

    MedlinePlus

    ... child may not be able to play contact sports because there's a risk that the spleen could rupture or hemorrhage. Certain forms of anemia (such as sickle cell disease) need other, more specific kinds of care and treatment. How Can I Prevent Iron-Deficiency Anemia in My Kids? Many kinds of anemia ...

  17. [Diagnosis and therapy of anemia in chronic diseases].

    PubMed

    Scudla, V; Adam, Z; Scudlová, M

    2001-06-01

    The article deals with contemporary views on anaemia associated with chronic diseases. The authors present the definition of this nosological unit, draw attention to its high incidence in clinical practice and fact that it is frequently mistaken for iron deficiency anaemia. The authors submit a review of the most frequent diseases which cause the development of this type of anaemia and analyze the role of activation of the system of cellular immunity, the monocyte-macrophage system, agents of the cytokine network in inhibition of proliferation and differentiation of erythroid precursors, reduced production of endogenous erythropoietin with a reduced sensitivity of erythroid progenitor cells to its action and impaired iron homeostasis and inhibition of its reutilization. Special attention is devoted to diagnostic and differential diagnostic criteria in relation to other types of anaemia caused by impaired haeme synthesis and some secondary multifactorially conditioned types of anaemia. More detailed attention is paid to the diagnostic value of evaluating serum levels of soluble transferrin receptors and explanation of the asset of calculation of the transferrin receptor/ferririn index as a sensitive indicator of latent sideropenia as well as the Fe-absorption test using low oral iron doses. Part of the paper is also an account of contemporary possibilities of treatment including the use of the recombinant form of human erythropoietin, and attention is drawn to the unsuitability and pitfalls of iron therapy in this type of anaemia.

  18. [Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia].

    PubMed

    Carrasco Sánchez, Francisco Javier; Recio Iglesias, Jesús; Grau Amorós, Jordi

    2014-03-01

    Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  19. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia.

    PubMed

    Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

    2015-12-25

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.

  20. Anemia and left ventricular hypertrophy with renal function decline and cardiovascular events in chronic kidney disease.

    PubMed

    Chang, Jer-Ming; Chen, Szu-Chia; Huang, Jiun-Chi; Su, Ho-Ming; Chen, Hung-Chun

    2014-03-01

    Anemia is a common complication in patients with chronic kidney disease (CKD), which may initiate or accelerate left ventricular hypertrophy (LVH). This study is designed to assess whether the coexistence of anemia and LVH is independently associated with the rate of renal function decline and increased cardiovascular events in patients with CKD stages 3 to 5. This longitudinal study enrolled 415 patients, who were classified into 4 groups according to sex-specific median values of hemoglobin and with/without LVH. The change in renal function was measured by estimated glomerular filtration rate slope. Cardiovascular events were defined as cardiovascular death, hospitalization for unstable angina, nonfatal myocardial infarction, sustained ventricular arrhythmia, hospitalization for congestive heart failure, transient ischemia attack, and stroke. The relative risk of cardiovascular events was analyzed by Cox's regression method. The estimated glomerular filtration rate slope was significantly lower in the group with lower hemoglobin and LVH than in the other groups (P ≤ 0.031). In addition, patients with lower hemoglobin and LVH were independently associated with increased cardiovascular events (hazard ratio, 4.269; 95% confidence interval, 1.402-13.000; P = 0.011). Our findings showed that the coexistence of anemia and LVH was independently associated with faster renal function decline and poor cardiovascular outcomes in patients with CKD. Assessments of serum hemoglobin level and LVH by echocardiography may help identify a high-risk group of poor renal and cardiovascular prognosis in patients with CKD stages 3 to 5.

  1. The relationship between anemia, liver disease, and hepcidin levels in hemodialysis patients with hepatitis.

    PubMed

    Zumrutdal, A; Sezgin, N

    2012-11-01

    We investigated the role of hepcidin in ameliorating anemia in hemodialysis patients with hepatitis. A total of 72 hemodialysis patients with hepatitis were classified according to their requirement of erythropoietin (EPO). Anemia parameters, C-reactive protein (CRP), and biochemical measurements were recorded along with the hepcidin. The number of patients receiving no EPO was higher among patients with liver disease when compared with those without liver disease (P = 0.002). The mean hepcidin levels of the patients who did not receive EPO did not differ statistically from those of the patients who received the maximum dose (P = 0.5). The hepcidin levels of patients with liver disease who received no EPO were lower compared to those patients without liver disease who received the maximum dose (P = 0.04). There was a positive correlation between hepcidin and mean platelet levels (r = 0.26, P = 0.027) and annual intravenous iron dose (r = 0.31, P = 0.007). In hemodialysis patients with hepatitis, liver disease may be one of the factors affecting erythropiesis, related with decreased hepcidin levels and iron hemostasis. Further studies are needed to verify these associations.

  2. A bidirectional YAC walk from the Norrie disease (NDP) locus

    SciTech Connect

    Black, G.C.; Zheng-Yi Chen; Craig, I.W.

    1995-02-10

    The region of Xp between DXS7 and the centromere contains the gene for Norrie disease in addition to the genes for several other ophthalmic disorders. A 650-kb YAC containing the loci MAOA, MAOB, and NDP has been used as the starting point for a bidirectional chromosomal walk. A contig of 16 YACs covering between 2 and 3 Mb has been developed in which the following markers/genes are located (in physical order): Xpter - DXS1201 (256ze5) - DXS6668 - DXS228 - DXS77 - DXS7 - MAOA - MAOB - FR12 (pseudogene) - NDP - DXS6670 - RRM2P3 - DXS6671 - DXS742 - Xcen. Seven new STSs are described both for end clones and for internal Alu PCR products from the contig. The contig contains the breakpoint of the t75-2ma-1b (t75) translocation, close to the 5{prime} end of the MAOB gene. 31 refs., 3 figs., 3 tabs.

  3. Chromosome substitution strain assessment of a Huntington's disease modifier locus.

    PubMed

    Ramos, Eliana Marisa; Kovalenko, Marina; Guide, Jolene R; St Claire, Jason; Gillis, Tammy; Mysore, Jayalakshmi S; Sequeiros, Jorge; Wheeler, Vanessa C; Alonso, Isabel; MacDonald, Marcy E

    2015-04-01

    Huntington's disease (HD) is a dominant neurodegenerative disorder that is due to expansion of an unstable HTT CAG repeat for which genome-wide genetic scans are now revealing chromosome regions that contain disease-modifying genes. We have explored a novel human-mouse cross-species functional prioritisation approach, by evaluating the HD modifier 6q23-24 linkage interval. This unbiased strategy employs C57BL/6J (B6J) Hdh(Q111) knock-in mice, replicates of the HD mutation, and the C57BL/6J-chr10(A/J)/NaJ chromosome substitution strain (CSS10), in which only chromosome 10 (chr10), in synteny with the human 6q23-24 region, is derived from the A/J (AJ) strain. Crosses were performed to assess the possibility of dominantly acting chr10 AJ-B6J variants of strong effect that may modulate CAG-dependent Hdh(Q111/+) phenotypes. Testing of F1 progeny confirmed that a single AJ chromosome had a significant effect on the rate of body weight gain and in Hdh(Q111) mice the AJ chromosome was associated subtle alterations in somatic CAG instability in the liver and the formation of intra-nuclear inclusions, as well as DARPP-32 levels, in the striatum. These findings in relatively small cohorts are suggestive of dominant chr10 AJ-B6 variants that may modify effects of the CAG expansion, and encourage a larger study with CSS10 and sub-strains. This cross-species approach may therefore be suited to functional in vivo prioritisation of genomic regions harbouring genes that can modify the early effects of the HD mutation.

  4. A Study of Human Leukocyte D Locus Related Antigens in Graves' Disease

    PubMed Central

    Farid, Nadir R.; Sampson, Laura; Noel, Elke P.; Barnard, John M.; Mandeville, Robert; Larsen, Bodil; Marshall, William H.; Carter, Nicholas D.

    1979-01-01

    An association between Graves' disease and the human leukocyte antigen (HLA) system has previously been reported. The disease was more strongly associated with the HLA D locus antigen Dw3 than with HLA B8. Products of the HLA D locus are determined by the interaction of test cells with standard typing lymphocytes, a technically difficult procedure. Recently, it has been possible to type serologically for D locus related (DRw) specificities on peripheral bone marrow-derived (B) lymphocytes. Blood B lymphocytes from 50 unrelated controls and 41 patients with Graves' disease were typed for seven HLA DRw specificities. 28 patients with Graves' disease (68%) were positive for DRw3, in contrast to 14 controls (28%); whereas only 21 patients (50%) were HLA B8 positive, compared with 13 (26%) controls. Thus, positivity for DRw3 afforded a relative risk for Graves' disease of 5.5, whereas that for HLA B8 amounted to 3.0. Additionally, a family with multiple cases of Graves' disease in which the disease was previously shown to be inherited with the haplotype, was linked to DRw2, which suggests that the susceptibility to the disease was inherited in association with that antigen. Two HLA B/glyoxalase recombination events were observed in this family; in both instances HLA DRw followed HLA B. This study thus demonstrates that the disease susceptibility gene for Graves' disease is in strong linkage disequilibrium with DRw3; however, it may be associated with other DRw specificities and inherited within family units in association with them. PMID:105012

  5. Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease: A nested case-control study

    PubMed Central

    Loutradis, Charalampos; Skodra, Alexandra; Georgianos, Panagiotis; Tolika, Panagiota; Alexandrou, Dimitris; Avdelidou, Afroditi; Sarafidis, Pantelis A

    2016-01-01

    AIM: To compare anemia prevalence between matched chronic kidney disease (CKD) patients with and without diabetes mellitus (DM) and to assess factors associated with anemia development. METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate (eGFR). Prevalence of anemia (hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia. RESULTS: The total prevalence of anemia was higher in diabetics (47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3 (53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a (60.4% vs 26.4%, P < 0.001), whereas it was non-significantly higher in Stage 4 (61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM (OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4 (Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron (OR = 0.976, 95%CI: 0.968-0.985 per mg/dL increase) were independently associated with anemia. CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts. PMID:27458564

  6. [Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus].

    PubMed

    Axer, H; Hüge, S; Wilhelm, C; Axer, M; Kunze, A; Reichenbach, J R; Freesmeyer, M; Kohlhase, J; Sauer, H; Bär, K-J

    2009-01-01

    We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

  7. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  8. Fixing the broken system of genetic locus symbols: Parkinson disease and dystonia as examples.

    PubMed

    Marras, Connie; Lohmann, Katja; Lang, Anthony; Klein, Christine

    2012-03-27

    Originally, locus symbols (e.g., DYT1) were introduced to specify chromosomal regions that had been linked to a familial disorder with a yet unknown gene. Symbols were systematically assigned in a numerical series to designate mapped loci for a specific phenotype or group of phenotypes. Since the system of designating and using locus symbols was originally established, both our knowledge and our techniques of gene discovery have evolved substantially. The current system has problems that are sources of confusion, perpetuate misinformation, and misrepresent the system as a useful reference tool for a list of inherited disorders of a particular phenotypic class. These include erroneously assigned loci, duplicated loci, missing symbols, missing loci, unconfirmed loci in a consecutively numbered system, combining causative genes and risk factor genes in the same list, and discordance between phenotype and list assignment. In this article, we describe these problems and their impact, and propose solutions. The system could be significantly improved by creating distinct lists for clinical and research purposes, creating more informative locus symbols, distinguishing disease-causing mutations from risk factors, raising the threshold of evidence prior to assigning a locus symbol, paying strict attention to the predominant phenotype when assigning symbols lists, and having a formal system for reviewing and continually revising the list that includes input from both clinical and genetics experts.

  9. Caregiver's Health Locus of Control and Medication Adherence in Sickle Cell Disease.

    PubMed

    Viswanathan, Kusum; Swaminathan, Neeraja; Viswanathan, Ramaswamy; Lakkaraja, Madhavi

    2015-03-01

    The authors would like to thank Dr. Morisky for giving us permission to use the Morisky Medication Adherence Scale To explore caregivers' Health Locus of Control's relationship to self-reported adherence to penicillin prophylaxis or hydroxyurea in children with sickle cell disease (SCD). A questionnaire-based study was conducted of caregivers of children with SCD who visited a comprehensive sickle cell center in an inner city hospital, who were either on penicillin prophylaxis or hydroxyurea or both. Multidimensional Health Locus of Control Scale (MHLC) and the Morisky Medication Adherence Scale (MMAS-8) questionnaires were used for the study. Caregivers of 43 children (27 on penicillin prophylaxis, 13 on hydroxyurea, and 3 on both) completed the MHLC and the MMAS-8. There was no significant difference in adherence between the penicillin and the hydroxyurea groups. The mean Powerful Others score of caregivers of the hydroxyurea only group (25.5+5.6) was higher than that of the penicillin only group (21.2+6.1, p=0.043). Regression analysis revealed an inverse relationship of Chance Locus of Control to adherence in the entire group (Beta = -0.306, R2=0.093, F[1,40]=4.12, p=0.049). Chance Locus of control may identify caregivers of children with SCD at risk for non-adherence to treatment. © 2015 National Medical Association. Published by Elsevier Inc. All rights reserved.

  10. Design and sample-size considerations in the detection of linkage disequilibrium with a disease locus

    SciTech Connect

    Olson, J.M.; Wijsman, E.M.

    1994-09-01

    The presence of linkage disequilibrium between closely linked loci can aid in the fine mapping of disease loci. The authors investigate the power of several designs for sampling individuals with different disease genotypes. As expected, haplotype data provide the greatest power for detecting disequilibrium, but, in the absence of parental information to resolve the phase of double heterozygotes, the most powerful design samples only individuals homozygous at the trait locus. For rare diseases, such a scheme is generally not feasible, and the authors also provide power and sample-size calculations for designs that sample heterozygotes. The results provide information useful in planning disequilibrium studies. 17 refs., 3 figs., 4 tabs.

  11. Iron refractory iron deficiency anemia: a heterogeneous disease that is not always iron refractory.

    PubMed

    Donker, Albertine E; Schaap, Charlotte C M; Novotny, Vera M J; Smeets, Roel; Peters, Tessa M A; van den Heuvel, Bert L P; Raphael, Martine F; Rijneveld, Anita W; Appel, Inge M; Vlot, Andre J; Versluijs, A Birgitta; van Gelder, Michel; Granzen, Bernd; Janssen, Mirian C H; Rennings, Alexander J M; van de Veerdonk, Frank L; Brons, Paul P T; Bakkeren, Dirk L; Nijziel, Marten R; Vlasveld, L Thom; Swinkels, Dorine W

    2016-12-01

    TMPRSS6 variants that affect protein function result in impaired matriptase-2 function and consequently uninhibited hepcidin production, leading to iron refractory iron deficiency anemia (IRIDA). This disease is characterized by microcytic, hypochromic anemia and serum hepcidin values that are inappropriately high for body iron levels. Much is still unknown about its pathophysiology, genotype-phenotype correlation, and optimal clinical management. We describe 14 different TMPRSS6 variants, of which 9 are novel, in 21 phenotypically affected IRIDA patients from 20 families living in the Netherlands; 16 out of 21 patients were female. In 7 out of 21 cases DNA sequencing and multiplex ligation dependent probe amplification demonstrated only heterozygous TMPRSS6 variants. The age at presentation, disease severity, and response to iron supplementation were highly variable, even for patients and relatives with similar TMPRSS6 genotypes. Mono-allelic IRIDA patients had a milder phenotype with respect to hemoglobin and MCV and presented significantly later in life with anemia than bi-allelic patients. Transferrin saturation (TSAT)/hepcidin ratios were lower in IRIDA probands than in healthy relatives. Most patients required parenteral iron. Genotype alone was not predictive for the response to oral iron. We conclude that IRIDA is a genotypically and phenotypically heterogeneous disease. The high proportion of female patients and the discrepancy between phenotypes of probands and relatives with the same genotype, suggest a complex interplay between genetic and acquired factors in the pathogenesis of IRIDA. In the absence of inflammation, the TSAT/hepcidin ratio is a promising diagnostic tool, even after iron supplementation has been given. Am. J. Hematol. 91:E482-E490, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches.

    PubMed

    Steinberg, Martin H

    2008-12-25

    The root cause of sickle cell disease is a single beta-globin gene mutation coding for the sickle beta-hemoglobin chain. Sickle hemoglobin tetramers polymerize when deoxygenated, damaging the sickle erythrocyte. A multifaceted pathophysiology, triggered by erythrocyte injury induced by the sickle hemoglobin polymer, and encompassing more general cellular and tissue damage caused by hypoxia, oxidant damage, inflammation, abnormal intracellular interactions, and reduced nitric oxide bioavailability, sets off the events recognized clinically as sickle cell disease. This disease is a group of related disorders where sickle hemoglobin is the principal hemoglobin species. All have varying degrees of chronic hemolytic anemia, vasculopathy, vasoocclusive disease, acute and chronic organ damage, and shortened life span. Its complex pathophysiology, of which we have a reasonable understanding, provides multiple loci for potential therapeutic intervention.

  13. A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

    PubMed Central

    Kniazeva, M; Chiang, M F; Morgan, B; Anduze, A L; Zack, D J; Han, M; Zhang, K

    1999-01-01

    Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4. PMID:10205271

  14. A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

    PubMed

    Kniazeva, M; Chiang, M F; Morgan, B; Anduze, A L; Zack, D J; Han, M; Zhang, K

    1999-05-01

    Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4.

  15. New expectations in the treatment of anemia in chronic kidney disease.

    PubMed

    López-Gómez, Juan M; Abad, Soraya; Vega, Almudena

    2016-01-01

    The new drugs developed for the treatment of anemia in chronic kidney disease patients, together with their mechanisms of action are reviewed. At present, many of them are already in advanced stages of clinical trials and is expected to be incorporated into the therapeutic arsenal in the coming years. The potential benefits and possible limitations are also described. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  16. The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

    PubMed Central

    2013-01-01

    Background Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). Methods This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. Results During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. Conclusions Renal anemia is associated with a more rapid evolution to CKD-4, and a higher

  17. Aplastic anemia.

    PubMed

    Usuki, Kensuke

    Treatments of aplastic anemia are comprised of supportive therapy and aplastic anemia-specific therapy aimed at restoring hematopoiesis. Supportive therapies include transfusion, G-CSF, and the administration of iron chelation agents, as well as dealing specifically with individual symptoms. Aplastic anemia-specific treatments given with the aim of achieving hematopoietic recovery include immunosuppressive therapy, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although transplantation provides complete recovery of hematopoiesis (cure), there is a risk of death due to transplant-related complications. The most effective immunosuppressive therapy is a combination of anti-thymocyte globulin and cyclosporine. This treatment is also effective against the secondary, drug-induced and hepatitis-associated forms of aplastic anemia. In the management of aplastic anemia, a treatment is selected from among these options depending on the disease severity and the age of the individual case. The thrombopoietin receptor agonist eltrombopag appears to be effective and to provide tri-lineage recovery of hematopoiesis in some cases. Indications for its use are expected to expand in Japan.

  18. Lafora disease is not linked to the Unverricht-Lundborg locus

    SciTech Connect

    Labauge, P.; Beck, C.; Bellet, H.; Baldy-Moulinier, M.; Malafosse, A.

    1995-02-27

    Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis. 16 refs., 2 figs., 2 tabs.

  19. Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease.

    PubMed

    Vlagopoulos, Panagiotis T; Tighiouart, Hocine; Weiner, Daniel E; Griffith, John; Pettitt, Dan; Salem, Deeb N; Levey, Andrew S; Sarnak, Mark J

    2005-11-01

    Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m(2). Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.

  20. Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014.

    PubMed

    Visconte, Valeria; Lindsley, R Coleman; Berlyne, Deborah

    2015-01-01

    Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD.

  1. Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: First multicenter, cross-sectional study.

    PubMed

    Li, Ya; Shi, Hao; Wang, Wei-Ming; Peng, Ai; Jiang, Geng-Ru; Zhang, Jin-Yuan; Ni, Zhao-Hui; He, Li-Qun; Niu, Jian-Ying; Wang, Nian-Song; Mei, Chang-Lin; Xu, Xu-Dong; Guo, Zhi-Yong; Yuan, Wei-Jie; Yan, Hai-Dong; Deng, Yue-Yi; Yu, Chen; Cen, Jun; Zhang, Yun; Chen, Nan

    2016-06-01

    This was the first multicenter, cross-sectional survey to assess the prevalence of anemia, patient awareness, and treatment status in China. Data of patients with chronic kidney disease (CKD; age, 18-75 years; both out- and inpatients) from 25 hospitals in Shanghai, seeking medical treatment at the nephrology department, were collected between July 1, 2012 and August 31, 2012. The prevalence, awareness, and treatment of anemia in patients with nondialysis CKD (ND-CKD) were assessed. Anemia was defined as serum hemoglobin (Hb) levels ≤12 g/dL in women and ≤13 g/dL in men. A total of 2420 patients with ND-CKD were included. Anemia was established in 1246 (51.5%) patients: 639 (51.3%) men and 607 (48.7%) women. The prevalence of anemia increased with advancing CKD stage (χtrend = 675.14, P < 0.001). Anemia was more prevalent in patients with diabetic nephropathy (68.0%) than in patients with hypertensive renal damage (56.6%) or chronic glomerulonephritis (46.1%, both P < 0.001). Only 39.8% of the anemic patients received treatment with erythropoietin and 27.1% patients received iron products; furthermore, 22.7% of the patients started receiving treatment when their Hb level reached 7 g/dL. The target-achieving rate (Hb at 11-12 g/dL) was only 8.2%. Of the 1246 anemia patients, only 7.5% received more effective and recommended intravenous supplementation. Anemia is highly prevalent in patients with ND-CKD in China, with a low target-achieving rate and poor treatment patterns. The study highlights the need to improve multiple aspects of CKD management to delay the progression of renal failure.

  2. NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia

    PubMed Central

    Wang, Xu; Yu, Suyun; Jia, Qi; Chen, Lichuan; Zhong, Jinqiu; Pan, Yanhong; Shen, Peiliang; Shen, Yin; Wang, Siliang; Wei, Zhonghong; Cao, Yuzhu; Lu, Yin

    2017-01-01

    NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools. Protein-protein interaction networks of CKD-related and putative NDQ targets were constructed, and 219 candidate targets were identified based on topological features. Pathway enrichment analysis showed that the candidate targets were mostly related to the TGF-β, the p38MAPK, and the erythropoietin (EPO) receptor signaling pathways, which are known contributors to renal fibrosis and/or renal anemia. A rat model of CKD was established to validate the drug-target mechanisms predicted by the systems pharmacology analysis. Experimental results confirmed that NDQ granules exerted therapeutic effects on CKD and its comorbidities, including renal anemia, mainly by modulating the TGF-β and EPO signaling pathways. Thus, the pharmacological actions of NDQ on CKD symptoms correlated well with in silico predictions. PMID:28915563

  3. NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia.

    PubMed

    Wang, Xu; Yu, Suyun; Jia, Qi; Chen, Lichuan; Zhong, Jinqiu; Pan, Yanhong; Shen, Peiliang; Shen, Yin; Wang, Siliang; Wei, Zhonghong; Cao, Yuzhu; Lu, Yin

    2017-08-22

    NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools. Protein-protein interaction networks of CKD-related and putative NDQ targets were constructed, and 219 candidate targets were identified based on topological features. Pathway enrichment analysis showed that the candidate targets were mostly related to the TGF-β, the p38MAPK, and the erythropoietin (EPO) receptor signaling pathways, which are known contributors to renal fibrosis and/or renal anemia. A rat model of CKD was established to validate the drug-target mechanisms predicted by the systems pharmacology analysis. Experimental results confirmed that NDQ granules exerted therapeutic effects on CKD and its comorbidities, including renal anemia, mainly by modulating the TGF-β and EPO signaling pathways. Thus, the pharmacological actions of NDQ on CKD symptoms correlated well with in silico predictions.

  4. Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

    SciTech Connect

    Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M.

    1997-03-31

    We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderately severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.

  5. Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses

    PubMed Central

    2013-01-01

    EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed. PMID:24289102

  6. Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.

    PubMed

    Bolfa, Pompei; Nolf, Marie; Cadoré, Jean-Luc; Catoi, Cornel; Archer, Fabienne; Dolmazon, Christine; Mornex, Jean-François; Leroux, Caroline

    2013-12-01

    EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed.

  7. Analysis of human chromosome 21 for a locus conferring susceptibility to Hirschsprung Disease

    SciTech Connect

    Bolk, S.; Duggan, D.J.; Chakravarti, A.

    1994-09-01

    It has been estimated that approximately 5% of patients diagnosed with Hirschsprung disease (HSCR), or aganglionic megacolon, have trisomy 21. Since the incidence of Hirschsprung disease is 1/5000 live births and the incidence of trisomy 21 is approximately 1/1000 live births, the observed occurrence of HSCR in trisomy 21 is fifty times higher than expected. We propose that at least one locus on chromosome 21 predisposes to HSCR. Although at fifty times elevated risk, only 1% of Down Syndrome cases have HSCR. Thus additional genes or genetic events are necessary for HSCR to manifest in patients with trisomy 21. Based on segregation analysis, Badner et al. postulated that recessive genes may be responsible for up to 80% of HSCR. We postulate that at least one such gene is on chromosome 21 and increased homozygosity for common recessive HSCR mutations may be one cause for the elevated risk of HSCR in cases of trisomy 21. To map such a chromosome 21 locus, we are searching for segments of human chromosome 21 which are identical by descent from the parent in whom non-disjunction occurred. These segments will arise either from meiosis I (followed by a crossover between the centromere and the locus) or from meiosis II (followed by no crossovers). Nine nuclear families with a proband diagnosed with HSCR and Down Syndrome have been genotyped for 18 microsatellite markers spanning human chromosome 21q. In all nine cases analyzed thus far, trisomy 21 resulted from maternal non-disjunction at meiosis I. At this point no single IBD region is apparent. Therefore, additional families are being ascertained and additional markers at high density are being genotyped to map the HSCR locus.

  8. Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson's Disease Locus.

    PubMed

    Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M; Heckman, Michael G; McCarthy, Allan; Soto-Ortolaza, Alexandra I; Walton, Ronald L; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W; Uitti, Ryan J; Wszolek, Zbigniew K; Ross, Owen A

    2015-01-01

    Genome-wide association studies (GWAS) in Parkinson's disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11-1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD.

  9. Epidural anesthesia for laparoscopic cholecystectomy in a patient with sickle cell anemia, beta thalassemia, and Crohn's disease -A case report-

    PubMed Central

    Özlü, Onur

    2012-01-01

    A 37-year-old woman diagnosed with sickle cell anemia (SCA), beta (+) thalassemia, Crohn's disease, and liver dysfunction was scheduled for laparoscopic cholecystectomy (LC) due to acute cholecystitis with gall bladder. Regional anesthesia was performed. An epidural catheter was inserted into the 9-10 thoracal epidural space and then 15 ml of 0.5% bupivacaine was injected through the catheter. The level of sensorial analgesia tested with pinprick test reached up to T4. Here we describe the first case of the combination of sickle cell anemia (SCA), beta (+) thalassemia, and Crohn's disease successful anesthetic management with attention to hemodynamics, particularly with regards to liver dysfunction. PMID:23115690

  10. Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients.

    PubMed

    Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

    2016-05-12

    Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD's acute inflammatory phase.

  11. Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

    PubMed Central

    Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

    2016-01-01

    Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

  12. Prevalence of chronic kidney disease and anemia in patients with coronary artery disease with normal serum creatinine undergoing percutaneous coronary interventions: relation to New York Heart Association class.

    PubMed

    Malyszko, Jolanta; Bachorzewska-Gajewska, Hanna; Malyszko, Jacek; Levin-Iaina, Nomy; Iaina, Adrian; Dobrzycki, Slawomir

    2010-08-01

    Kidney disease and cardiovascular disease seem to be lethally synergistic and both are approaching the epidemic level. A reduced glomerular filtration rate is associated with increased mortality risk in patients with heart failure. Many patients with congestive heart failure are anemic. Anemia is very often associated with chronic kidney disease. To assess--in relation to New York Heart Association class--the prevalence of anemia and chronic kidney disease in patients with normal serum creatinine in a cohort of 526 consecutive patients with coronary artery disease undergoing percutaneous coronary interventions. GFR was estimated using the simplified MDRD formula, the Cockcroft-Gault formula, the Jeliffe and the novel CKD-EPI formula. According to the WHO definition the prevalence of anemia in our study was 21%. We observed a progressive decline in GFR and hemoglobin concentration together with a rise in NYHA class. Significant correlations were observed between eGFR and systolic blood pressure, diastolic blood pressure, age, NYHA class, complications of PCI, including bleeding, and major adverse cardiac events. The prevalence of anemia and chronic kidney disease is high in patients undergoing PCI despite normal serum creatinine, particularly in higher NYHA class. Lower eGFR and hemoglobin are associated with more complications, including bleeding after PCI and higher prevalence of major adverse cardiac events. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality.

  13. Anemia of inflammation.

    PubMed

    Nemeth, Elizabeta; Ganz, Tomas

    2014-08-01

    Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. It is diagnosed when serum iron concentrations are low despite adequate iron stores, as evidenced by serum ferritin that is not low. In the setting of inflammation, it may be difficult to differentiate AI from iron deficiency anemia, and the 2 conditions may coexist. Treatment should focus on the underlying disease. Recent advances in molecular understanding of AI are stimulating the development of new pathophysiologically targeted experimental therapies.

  14. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model

    PubMed Central

    Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

    2017-01-01

    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. PMID:28143953

  15. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

    PubMed

    Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

    2017-02-01

    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis.

  16. [Maternal Crohn's disease-related vitamin B12 deficient megaloblastic anemia in an infant].

    PubMed

    Ohyama, Wataru; Yamaoka, Masayoshi; Yokoi, Kentaro; Iwahashi, Megumi; Inage, Yuka; Arihiro, Seiji; Koganei, Kazutaka; Sugita, Akira; Ida, Hiroyuki; Akiyama, Masaharu

    2016-01-01

    We report an 11-month-old breast-fed boy with feeding difficulties, lethargy, and developmental delay. Blood examination showed pancytopenia and decreased serum levels of vitamin B12. Anisocytosis and poikilocytes were detected in his peripheral blood, and increased megaloblastosis without leukemic cells was detected in his bone marrow. After the diagnosis of megaloblastic anemia due to vitamin B12 deficiency, symptoms were improved by vitamin B12 administration. Further investigation of the mother identified Crohn's disease and suggested that the supply of vitamin B12 from the mother to the infant, via the placenta during pregnancy and via breast milk after birth, was decreased due to impaired absorption of vitamin B12 in the mother's small intestine. Magnetic resonance imaging of the boy's brain on admission showed cerebral cortex atrophy which had improved by the age of 1 year and 10 months after vitamin B12 treatment, though developmental delay was still evident at the age of 3 years. Infantile vitamin B12 deficiency often presents with nonspecific manifestations, such as developmental delay and failure to thrive, in addition to anemia and is thus not easily diagnosed. To prevent severe neurological sequelae, this condition must be rapidly diagnosed, because a prolonged duration increases the risk of permanent disabilities.

  17. Clinical outcomes of erythropoietin use in heart failure patients with anemia of chronic kidney disease.

    PubMed

    Jackevicius, Cynthia A; Fan, Cindy Shutieng; Warner, Alberta

    2014-05-01

    Anemia and chronic kidney disease are common disorders in heart failure (HF) patients and are associated with increased morbidity and mortality. This study assessed clinical outcomes associated with erythropoietin (EPO) treatment in this cardiorenal anemia syndrome (CRAS) population. This was a retrospective cohort study of Veterans Affairs patients with CRAS from January 2003 to December 2006. The primary outcome was a composite of death, acute coronary syndrome (ACS), HF, and stroke. Multiple Cox regression modeling was used to evaluate the outcome in patients prescribed (n = 213) and not prescribed EPO (n = 1845). Adjusted incidence of mortality was statistically significantly higher in EPO than in non-EPO users (33.8% vs 19.7%; hazard ratio 1.40, 95% confidence interval 1.06-1.85; P = .02). The unadjusted composite of cardiovascular events/death was higher in the EPO group, but not statistically significant when adjusted for confounders (P = .12). Crude ACS events were documented in 18.8% and 10.8% patients (P = .001), and stroke events occurred in 22.5% and 18.3% patients (P = .14) in EPO and non-EPO groups, respectively. We found that in CRAS patients, EPO use was associated with increased risk of mortality and a trend toward increased cardiovascular events. Therefore, clinicians considering EPO use in CRAS patients should assess whether any potential benefits outweigh the risks of use. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases.

    PubMed

    Chalhoub, S; Langston, C E; Farrelly, J

    2012-01-01

    Anemia is present in 30-65% in cats with chronic kidney disease (CKD) and few long-term treatment options exist. Darbepoetin is effective in treating anemia of kidney disease in humans and may be used in cats. To evaluate the use of darbepoetin, a recombinant analog of human erythropoietin, to stimulate erythropoiesis, and to effectively treat anemia of kidney disease in cats. Twenty-five of 66 cats that received ≥ 2 doses of darbepoetin at the Animal Medical Center between January 2005 and December 2009 were included in this study. Cats were included in the study if they received darbepoetin and follow-up data were available for at least 56 days and had CKD as a primary clinical diagnosis. Cats were excluded if they were treated with darbepoetin but did not have kidney disease. Response to treatment was defined as reaching or exceeding a target packed red blood cell volume or hematocrit of 25%. Fourteen of 25 cats responded. Thirteen of those 14 cats received a dosage of 1 μg/kg/wk or higher. Presumptive adverse effects included vomiting, hypertension, seizures, and fever. Darbepoetin is effective for treatment of anemia of kidney disease in cats. Pure red cell aplasia appears to be less common with darbepoetin than with epoetin usage. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  19. [Sideroblastic anemias].

    PubMed

    Matthes, T

    2006-01-01

    Sideroblastic anemias are a heterogenous group of disorders characterized by the presence of sideroblasts in the bone marrow aspirate. Current classification schemes distinguish between diseases of the heme synthesis pathway and diseases of other mitochondrial pathways which can either be of primary origin (defects in mitochondrial DNA) or of secondary origin (defects in nuclear DNA). Although several distinct hereditary forms exist, sideroblastic anemias are most frequently acquired diseases and belong to the group of myelodysplastic syndromes with the propensity to develop into overt leukemia. Treatment is mainly supportive (vitamins, blood transfusions, cytokines) and only rarely are bone marrow transplantations performed. The molecular defects of a few hereditary forms have already been elucidated, but the genes involved in the acquired forms are still largely unknown.

  20. [Iron dysregulation and anemias].

    PubMed

    Ikuta, Katsuya

    2015-10-01

    Most iron in the body is utilized as a component of hemoglobin that delivers oxygen to the entire body. Under normal conditions, the iron balance is tightly regulated. However, iron dysregulation does occasionally occur; total iron content reductions cause iron deficiency anemia and overexpression of the iron regulatory peptide hepcidin disturbs iron utilization resulting in anemia of chronic disease. Conversely, the presence of anemia may ultimately lead to iron overload; for example, thalassemia, a common hereditary anemia worldwide, often requires transfusion, but long-term transfusions cause iron accumulation that leads to organ damage and other poor outcomes. On the other hand, there is a possibility that iron overload itself can cause anemia; iron chelation therapy for the post-transfusion iron overload observed in myelodysplastic syndrome or aplastic anemia improves dependency on transfusions in some cases. These observations reflect the extremely close relationship between anemias and iron metabolism.

  1. Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease.

    PubMed

    Eriksson, D; Bianchi, M; Landegren, N; Nordin, J; Dalin, F; Mathioudaki, A; Eriksson, G N; Hultin-Rosenberg, L; Dahlqvist, J; Zetterqvist, H; Karlsson, Å; Hallgren, Å; Farias, F H G; Murén, E; Ahlgren, K M; Lobell, A; Andersson, G; Tandre, K; Dahlqvist, S R; Söderkvist, P; Rönnblom, L; Hulting, A-L; Wahlberg, J; Ekwall, O; Dahlqvist, P; Meadows, J R S; Bensing, S; Lindblad-Toh, K; Kämpe, O; Pielberg, G R

    2016-12-01

    Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  2. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology.

    PubMed

    Bradshaw, Elizabeth M; Chibnik, Lori B; Keenan, Brendan T; Ottoboni, Linda; Raj, Towfique; Tang, Anna; Rosenkrantz, Laura L; Imboywa, Selina; Lee, Michelle; Von Korff, Alina; Morris, Martha C; Evans, Denis A; Johnson, Keith; Sperling, Reisa A; Schneider, Julie A; Bennett, David A; De Jager, Philip L

    2013-07-01

    In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P(joint) = 1.3 × 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

  3. The genetic locus for free sialic acid storage disease maps to the long arm of chromosome 6.

    PubMed Central

    Haataja, L.; Schleutker, J.; Laine, A. P.; Renlund, M.; Savontaus, M. L.; Dib, C.; Weissenbach, J.; Peltonen, L.; Aula, P.

    1994-01-01

    Salla disease (SD), or adult-type free sialic acid storage disease, is an autosomal recessive lysosomal storage disorder characterized by impaired transport of free sialic acid across the lysosomal membrane and severe psychomotor retardation. Random linkage analysis of a sample of 27 Finnish families allowed us to localize the SD locus to the long arm of chromosome 6. The highest lod score of 8.95 was obtained with a microsatellite marker of locus D6S286 at theta = .00. Evidence for linkage disequilibrium was observed between the SD locus and the alleles of three closely linked markers, suggesting that the length of the critical region for the SD locus is in the order of 190 kb. PMID:8198127

  4. Iron Deficiency Anemia in Relation to Respiratory Disease and Social Behaviors In Low-Income Infants in France.

    ERIC Educational Resources Information Center

    Honig, Alice Sterling

    1993-01-01

    Examined a sample of 177 infants (age 9 through 12 months) with iron deficiency anemia (IDA) from low-income French, African, and North African Muslim families in Paris. Found a higher than normal incidence of otitis media and respiratory diseases such as bronchitis among the infants. Also examined the relationship between infant IDA and child…

  5. Iron Deficiency Anemia in Relation to Respiratory Disease and Social Behaviors In Low-Income Infants in France.

    ERIC Educational Resources Information Center

    Honig, Alice Sterling

    1993-01-01

    Examined a sample of 177 infants (age 9 through 12 months) with iron deficiency anemia (IDA) from low-income French, African, and North African Muslim families in Paris. Found a higher than normal incidence of otitis media and respiratory diseases such as bronchitis among the infants. Also examined the relationship between infant IDA and child…

  6. Intestine-specific Disruption of Hypoxia-inducible Factor (HIF)-2α Improves Anemia in Sickle Cell Disease.

    PubMed

    Das, Nupur; Xie, Liwei; Ramakrishnan, Sadeesh K; Campbell, Andrew; Rivella, Stefano; Shah, Yatrik M

    2015-09-25

    Sickle cell disease (SCD) is caused by genetic defects in the β-globin chain. SCD is a frequently inherited blood disorder, and sickle cell anemia is a common type of hemoglobinopathy. During anemia, the hypoxic response via the transcription factor hypoxia-inducible factor (HIF)-2α is highly activated in the intestine and is essential in iron absorption. Intestinal disruption of HIF-2α protects against tissue iron accumulation in iron overload anemias. However, the role of intestinal HIF-2α in regulating anemia in SCD is currently not known. Here we show that in mouse models of SCD, disruption of intestinal HIF-2α significantly decreased tissue iron accumulation. This was attributed to a decrease in intestinal iron absorptive genes, which were highly induced in a mouse model of SCD. Interestingly, disruption of intestinal HIF-2α led to a robust improvement in anemia with an increase in RBC, hemoglobin, and hematocrit. This was attributed to improvement in RBC survival, hemolysis, and insufficient erythropoiesis, which is evident from a significant decrease in serum bilirubin, reticulocyte counts, and serum erythropoietin following intestinal HIF-2α disruption. These data suggest that targeting intestinal HIF-2α has a significant therapeutic potential in SCD pathophysiology.

  7. Unusual Anemias.

    PubMed

    Daughety, Molly Maddock; DeLoughery, Thomas G

    2017-03-01

    Many processes lead to anemia. This review covers anemias that are less commonly encountered in the United States. These anemias include hemoglobin defects like thalassemia, bone marrow failure syndromes like aplastic anemia and pure red cell aplasia, and hemolytic processes such as paroxysmal nocturnal hemoglobinuria. The pathogenesis, diagnostic workup, and treatment of these rare anemias are reviewed.

  8. Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

    PubMed Central

    Davis-Ajami, Mary Lynn; Wu, Jun; Downton, Katherine; Ludeman, Emilie; Noxon, Virginia

    2014-01-01

    Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L) or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L). This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility. PMID:24790409

  9. Sickle Cell Anemia

    MedlinePlus

    Sickle cell anemia is a disease in which your body produces abnormally shaped red blood cells. The cells are shaped like a crescent or sickle. They don' ... problem causes sickle cell anemia. People with the disease are born with two sickle cell genes, one ...

  10. Measurement of reticulocyte and red blood cell indices in the evaluation of anemia in inflammatory bowel disease.

    PubMed

    Oustamanolakis, Pantelis; Koutroubakis, Ioannis E; Messaritakis, Ippokratis; Kefalogiannis, Georgios; Niniraki, Maria; Kouroumalis, Elias A

    2011-08-01

    The commonest types of anemia in inflammatory bowel disease (IBD) are iron deficiency (IDA) and anemia of chronic disease. The differentiation between these two conditions is important for the management of the patient. The aim of this study was to investigate the usefulness of reticulocyte and red blood cell indices in the evaluation of anemia in IBD. One hundred IBD patients [49 ulcerative colitis (UC), 51 Crohn's disease (CD)] and 102 healthy controls were enrolled. Measurement of reticulocyte and red blood cell indices was performed using the Coulter LH780 Hematology Analyzer (Beckman Coulter). Additionally, serum levels of ferritin, transferrin saturation (Tsat) and soluble transferrin receptor (sTfR) were analyzed in all patients and controls. The prevalence of anemia was 41.2% for UC and 42.9% for CD, whereas 30 IBD patients (30%) had IDA. Red cell Distribution Width (RDW), Red blood cell Size Factor (RSF), and Reticulocyte Distribution Width-Coefficient of Variation (RDWR-CV) were found significantly correlated with both Tsat and sTfR but not with ferritin levels. Patients with IDA had significantly higher RDW and RDWR-CV and significantly lower RSF levels compared with those without IDA. High values of RDW (sensitivity 93%, specificity 81%) and low values of RSF (sensitivity 83%, specificity 82%) were the best markers for the diagnosis of IDA. Both RDWR-CV and RDWR-SD were significantly correlated with disease activity and CRP levels. RDW, RSF and RDWR, could be useful markers for the evaluation of anemia and disease activity in IBD. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  11. ATP5H/KCTD2 locus is associated with Alzheimer's disease risk

    PubMed Central

    Boada, M; Antúnez, C; Ramírez-Lorca, R; DeStefano, A L; González-Pérez, A; Gayán, J; López-Arrieta, J; Ikram, M A; Hernández, I; Marín, J; Galán, J J; Bis, J C; Mauleón, A; Rosende-Roca, M; Moreno-Rey, C; Gudnasson, V; Morón, F J; Velasco, J; Carrasco, J M; Alegret, M; Espinosa, A; Vinyes, G; Lafuente, A; Vargas, L; Fitzpatrick, A L; Launer, L J; Sáez, M E; Vázquez, E; Becker, J T; López, O L; Serrano-Ríos, M; Tárraga, L; van Duijn, C M; Real, L M; Seshadri, S; Ruiz, A

    2014-01-01

    To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10−6 were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10−7 in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10−9). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation. PMID:23857120

  12. Pernicious Anemia

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Pernicious Anemia? Pernicious anemia (per-NISH-us uh-NEE-me-uh) is ... nervous system working properly. People who have pernicious anemia can't absorb enough vitamin B12 from food. ...

  13. [Fatigue and anemia].

    PubMed

    Ivanova, K; Zeller, A

    2009-12-02

    We herein report on an 80-year old male patient with a history of muscle weakness, fatigue and weight loss since several months. Because of a pathologic synacthen test in combination with decreased levels of ACTH, we diagnosed a secondary chronic adrenal insufficiency. Because of a normochromic, normocytic, and hypo-proliferative anemia, bone marrow puncture was performed, showing an anemia of chronic disease. We initiated hydrocortisone and anemia and patients' symptoms were fully reconstituted.

  14. MAVS is not a Likely Susceptibility Locus for Addison's Disease and Type 1 Diabetes.

    PubMed

    Zurawek, Magdalena; Fichna, Marta; Kazimierska, Marta; Fichna, Piotr; Dzikiewicz-Krawczyk, Agnieszka; Przybylski, Grzegorz; Ruchala, Marek; Nowak, Jerzy

    2017-06-01

    Mitochondrial antiviral signaling (MAVS) protein is an intracellular adaptor molecule, downstream of viral sensors, retinoid acid-inducible gene I (RIG-I)-like receptors (RLRs). Impaired antiviral cell signaling might contribute to autoimmunity. Studies have recently shown variations in genes encoding RLRs as risk factors for autoimmune diseases. We investigated whether MAVS coding polymorphisms are associated with Addison's disease (AD) and type 1 diabetes (T1D) in Polish population. We genotyped 140 AD, 532 T1D patients and 600 healthy controls for MAVS rs17857295, rs7262903, rs45437096 and rs7269320. Genotyping was performed by TaqMan assays. Distribution of the MAVS genotypes and alleles did not reveal significant differences between patients and controls (p > 0.05). This analysis did not indicate the association of the MAVS locus with susceptibility to AD and T1D.

  15. A locus of group A Streptococcus involved in invasive disease and DNA transfer.

    PubMed

    Hidalgo-Grass, Carlos; Ravins, Miriam; Dan-Goor, Mary; Jaffe, Joseph; Moses, Allon E; Hanski, Emanuel

    2002-10-01

    Group A streptococcus (GAS) causes diseases ranging from benign to severe infections such as necrotizing fasciitis (NF). The reasons for the differences in severity of streptococcal infections are unexplained. We developed the polymorphic-tag-lengths-transposon-mutagenesis (PTTM) method to identify virulence genes in vivo. We applied PTTM on an emm14 strain isolated from a patient with NF and screened for mutants of decreased virulence, using a mouse model of human soft-tissue infection. A mutant that survived in the skin but was attenuated in its ability to reach the spleen and to cause a lethal infection was identified. The transposon was inserted into a small open reading frame (ORF) in a locus termed sil, streptococcal invasion locus. sil contains at least five genes (silA-E) and is highly homologous to the quorum-sensing competence regulons of Streptococcus pneumoniae. silA and silB encode a putative two-component system whereas silD and silE encode two putative ABC transporters. silC is a small ORF of unknown function preceded by a combox promoter. Insertion and deletion mutants of sil had a diminished lethality in the animal model. Virulence of a deletion mutant of silC was restored when injected together with the avirulent emm14-deletion mutant, but not when these mutants were injected into opposite flanks of a mouse. DNA transfer between these mutants occurred in vivo but could not account for the complementation of virulence. DNA exchange between the emm14-deletion mutant and mutants of sil occurred also in vitro, at a frequency of approximately 10-8 for a single antibiotic marker. Whereas silC and silD mutants exchanged markers with the emm14 mutant, silB mutant did not. Thus, we identified a novel locus, which controls GAS spreading into deeper tissues and could be involved in DNA transfer.

  16. Positional cloning of the chromosome 14 Alzheimer`s disease locus

    SciTech Connect

    Clark, R.F.; Korenblat, K.M.; Goate, A.M.

    1994-09-01

    Genetic linkage analysis had indicated a locus for familial early-onset Alzheimer`s disease (FAD) on chromosome 14 at q24.3. The FAD locus has been shown previously to lie between the dinucleotide markers D14S61 and D14S63, a genetic distance of approximately 13 cM. We are currently attempting to identify the gene using a positional cloning strategy. The first step towards the isolation and characterization of this locus was the construction of an overlapping YAC contig covering the entire region. Over forty YACs which map to this region have been isolated from the St. Louis and CEPH libraries by a combination of YAC end sequence walking and sequence tagged site mapping. Our contig fully spans the complete domain, encompassing all genetic markers non-recombinant with FAD (i.e. D14S76, D14S43, D14S71, D14S77) and the two nearest flanking FAD-recombinant markers. With restriction mapping of the domain, we can determine the exact size of the region. As a second step, the YACs in this contig are currently being inspected for expressed sequences by exon trapping, initially on those YACs known to be nonchimeric. We have currently made exon-trapped libraries from YACs that have the markers D14S76 and D14S43. Sequence analysis of these libraries indicates that a trapped exon is identified on average for each 30 kb of YAC DNA. The trapped exons are being screened to identify likely candidate genes, which will be examined for mutations in FAD families.

  17. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

    PubMed

    Cario, Holger; Smith, Desirée E C; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

    2011-02-11

    The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate.

  18. Dihydrofolate Reductase Deficiency Due to a Homozygous DHFR Mutation Causes Megaloblastic Anemia and Cerebral Folate Deficiency Leading to Severe Neurologic Disease

    PubMed Central

    Cario, Holger; Smith, Desirée E.C.; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

    2011-01-01

    The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate. PMID:21310277

  19. Prevalence and prognosis of mild anemia in non-dialysis chronic kidney disease: a prospective cohort study in outpatient renal clinics.

    PubMed

    De Nicola, Luca; Minutolo, Roberto; Chiodini, Paolo; Zamboli, Pasquale; Cianciaruso, Bruno; Nappi, Felice; Signoriello, Simona; Conte, Giuseppe; Zoccali, Carmine; SIN-TABLE CDK Study Group

    2010-01-01

    we evaluated prevalence and prognosis of mild anemia, defined as Hb (g/dl) 11-13.5 in males and 11-12 in females, in a prospective cohort of stage 3-5 chronic kidney disease (CKD) patients. we enrolled 668 consecutive patients in 25 renal clinics during 2003. Patients with frank anemia (Hb <11 or erythropoiesis-stimulating agents) at enrolment were excluded. Mild anemia was evaluated at two visits planned with an interval of 18 ± 6 months to identify four categories: no anemia at both visits, mild anemia at visit 1 resolving at visit 2 (RES), mild anemia persisting at both visits (PER), and progression from no anemia or mild anemia at visit 1 to mild or frank anemia at visit 2 (PRO). mild anemia was present in 41.3% at visit 1 and 34.1% at visit 2. We identified PER in 22% patients, RES in 10%, and PRO in 26%. In the subsequent 40 months, 125 patients developed end-stage renal disease (ESRD) and 94 died. At competing risk model, PER predicted ESRD (hazard ratio, HR, 1.82, 95% confidence interval, CI, 1.01-3.29) while PRO predicted both ESRD (HR 1.81, 95% CI 1.02-3.23) and death (HR 1.87, 95% CI 1.04-3.37). in non-dialysis chronic kidney disease, mild anemia is prevalent and it is a marker of risk excess when persistent or progressive over time. 2010 S. Karger AG, Basel.

  20. Oxidative stress during erythropoietin hyporesponsiveness anemia at end stage renal disease: Molecular and biochemical studies

    PubMed Central

    Khalil, Samar K.M.; Amer, H.A.; El Behairy, Adel M.; Warda, Mohamad

    2016-01-01

    Inflammation and oxidative stress are two faces of one coin in end stage renal disease patients (ESRD) on maintenance hemodialysis. Their interconnection induces anemia complicated with erythropoietin hyporesponsiveness. The biochemical bases behind the resistance to erythropoietin therapy with frequent hemoglobinemia, oxidative stress and iron status have not been fully understood. Here two equal groups (40 patients each) of responders and non-responders to recombinant human erythropoietin therapy (higher than 300 IU/kg/wk of epoetin) were investigated. Hematological and biochemical analyses of collected blood and serum samples were performed along with serum electrophoretic protein footprinting. The leukocytic DNA fragmentation was used to evaluate the degree of oxidative insult. The good responders showed lower erythrocyte malondialdehyde (E-MDA) level and less DNA fragmentation of circulating leukocytes than poor responders with elevated hemoglobin, albumin, A/G ratio, total iron, and ferritin levels. Contrariwise, lower erythrocyte superoxide dismutase (E-SOD) and catalase activities in EPO poor responder group were noticed. Neither other serum constituents nor electrophoretic protein pattern showed any difference between the two groups. There were higher levels of inflammatory markers, interleukin-6 (IL6) and C-reactive protein (CRP) in EPO poor responder than good responder. The negative correlations between Hb and both IL6 and CRP levels in the present data remotely indicate a positive correlation between inflammatory markers and severity of anemia. A direct correlation between Hb and antioxidant enzymes (E-SOD and catalase) was noticed, while inverse correlation with E-MDA was recorded. The study proved that oral supplementation of vitamin C to ESRD patients might mitigate the previously elevated serum MDA level in these patients. PMID:27222740

  1. Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study

    PubMed Central

    Kim, Yung Ly; Kim, Hyunwook; Kwon, Young Eun; Ryu, Dong-Ryeol; Lee, Mi Jung; Park, Kyung Sook; Ryu, Han Jak; Park, Jung Tak; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun

    2016-01-01

    Purpose Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. Materials and Methods We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. Results Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: β=0.263, p<0.001; age: β=0.122, p=0.010; ESA dose: β=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091–13.632; p=0.036). Conclusion 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients. PMID:27401647

  2. Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study.

    PubMed

    Kim, Yung Ly; Kim, Hyunwook; Kwon, Young Eun; Ryu, Dong Ryeol; Lee, Mi Jung; Park, Kyung Sook; Ryu, Han Jak; Park, Jung Tak; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae Hyun; Kang, Shin Wook

    2016-09-01

    Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: β=0.263, p<0.001; age: β=0.122, p=0.010; ESA dose: β=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.

  3. Prevalence of anemia according to stage of chronic kidney disease in a large screening cohort of Japanese.

    PubMed

    Kohagura, Kentaro; Tomiyama, Nozomi; Kinjo, Kozen; Takishita, Shuichi; Iseki, Kunitoshi

    2009-12-01

    The prevalence of chronic kidney disease (CKD) is high in developed countries, including Japan. However, little is known about the prevalence of anemia according to the estimated glomerular filtration rate (eGFR) among Japanese. We studied screenees on the Okinawa General Health Maintenance Association (OGHMA) registry in 1993 (N = 94,602; 54,848 women and 39,754 men) who had both serum creatinine and hematocrit data. Anemia was defined as follows: hematocrit level <40% in men, <32% in women aged <50 years, and <35% in women aged >or=50 years. GFR was estimated using a new Japanese equation: eGFR (ml/min per 1.73 m(2)) = 194 x serum creatinine(1.094) x age(0.287) x 0.739 (if female). The prevalence of anemia clearly increased as CKD progressed below an eGFR of 60 ml/min per 1.73 m(2) in both genders. Logistic analysis adjusted with body mass index and older age (>or=70 years) revealed that the odds ratio for complications of anemia was significantly increased below an eGFR of 45 ml/min per 1.73 m(2) in women and 90 ml/min per 1.73 m(2) in men. The association of lower kidney function with anemia was found to be more prevalent: adjusted odds ratio >or=2.0, from approximately 50 ml/min per 1.73 m(2). The present study suggested that there might be as many as 1,000,000 people with CKD stage 3-5 complicated with anemia in Japan.

  4. A major effect quantitative trait locus for whirling disease resistance identified in rainbow trout (Oncorhynchus mykiss)

    PubMed Central

    Baerwald, M R; Petersen, J L; Hedrick, R P; Schisler, G J; May, B

    2011-01-01

    Whirling disease, caused by the pathogen Myxobolus cerebralis, leads to skeletal deformation, neurological impairment and under certain conditions, mortality of juvenile salmonid fishes. The disease has impacted the propagation and survival of many salmonid species over six continents, with particularly negative consequences for rainbow trout. To assess the genetic basis of whirling disease resistance in rainbow trout, genome-wide mapping was initiated using a large outbred F2 rainbow trout family (n=480) and results were confirmed in three additional outbred F2 families (n=96 per family). A single quantitative trait locus (QTL) region on chromosome Omy9 was identified in the large mapping family and confirmed in all additional families. This region explains 50–86% of the phenotypic variance across families. Therefore, these data establish that a single QTL region is capable of explaining a large percentage of the phenotypic variance contributing to whirling disease resistance. This is the first genetic region discovered that contributes directly to the whirling disease phenotype and the finding moves the field closer to a mechanistic understanding of resistance to this important disease of salmonid fish. PMID:21048672

  5. Linkage disequilibrium utilized to establish a refined genetic position of the Salla disease locus on 6q14-q15

    SciTech Connect

    Schleutker, J.; Laine, A.P.; Haataja, L. |

    1995-05-20

    Salla disease (SD), an inherited free sialic acid storage disorder, is caused by impaired transport of free sialic acid across the lyosomal membrane. Clinical characteristics of the disease include severe psychomotor retardation and some neurological abnormalities. The authors report detailed linkage analyses of 50 Finnish SD families that localize the SD disease gene to a refined chromosomal area on 6q14-q15. The highest lod score of 17.30 was obtained with a microsatellite marker of locus D6S280. When linkage disequilibrium was adopted in the linkage analyses, they could further assign the SD locus to the immediate vicinity of marker locus D6S406. Linkage disequilibrium facilitated further restriction of the critical chromosomal region to approximately 80 kb, well within the limits of positional cloning techniques. 31 refs., 3 figs., 3 tabs.

  6. Distinguishing anemia and iron deficiency of heart failure: signal for severity of disease or unmet therapeutic need?

    PubMed

    Beavers, Craig J; Alburikan, Khalid A; Rodgers, Jo E; Dunn, Steven P; Reed, Brent N

    2014-07-01

    Despite advances in the management of heart failure (HF), quality of life and other outcomes remain suboptimal for many patients. Anemia and iron deficiency are comorbidities associated with adverse outcomes, although their pathophysiology in the setting of HF is not entirely understood. Anemia and iron deficiency may exist independently and may be a consequence of the systemic inflammatory state characterized by chronic HF. However, it is unclear whether serum hemoglobin concentrations and other hematologic parameters serve as markers for the severity of disease or represent novel therapeutic targets. Research in this area has focused primarily on therapies known to be effective for these conditions in other chronic disease states with similar pathophysiologic features (e.g., end-stage renal disease). Despite its many practical advantages, minimal evidence exists to support the use of oral iron supplementation in this setting. In contrast, intravenous iron has been the subject of several recent investigations, demonstrating improvements in both surrogate and clinical end points, although benefits seem to be the most substantial in patients with concomitant anemia. Erythropoietin-stimulating agents demonstrated early promise in retrospective analyses and small prospective trials, but their benefit was outweighed by a lack of improvement in clinical outcomes and an excess number of thromboembolic events in the largest trial of patients with anemia and HF to date. For acute symptomatic anemia, blood transfusion may be considered, although few trials have included patients with HF, and caution must be exerted in those who are hemodynamically unstable. Based on the currently available evidence, treatment of iron deficiency appears to confer benefit in patients with HF, whereas strategies aimed at improving hemoglobin alone do not. Included is a review of the pathophysiology of these conditions in the setting of HF, clinical trials evaluating pharmacologic therapy, and

  7. Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15

    SciTech Connect

    Kohrman, D.C.; Plummer, N.W.; Schuster, T.

    1995-03-20

    Homozygous transgenic mice from line A4 have an early-onset progressive neuromuscular disorder characterized by paralysis of the rear limbs, muscle atrophy, and lethality by 4 weeks of age. The transgene insertion site was mapped to distal chromosome 15 close to the locus motor endplate disease (med). The sequence of mouse DNA flanking the insertion site junctions was determined. A small (<20 kb) deletion was detected at the insertion site, with no evidence of additional rearrangement of the chromosomal DNA. Noncomplementation of the transgene-induced mutation and med was demonstrated in a cross with med{sup J}/ + mice. The new allele is designated med{sup TgNA4Bs}(med{sup tg}). The homologous human locus MED was assigned to chromosome 12. Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation. The transgene-induced allele provides molecular access to the med gene, whose function is required for synaptic transmission at the neuromuscular junction and long-term survival of cerebellar Purkinje cells. 49 refs., 5 figs., 1 tab.

  8. Congenital Hemolytic Anemia.

    PubMed

    Haley, Kristina

    2017-03-01

    Red blood cell (RBC) destruction can be secondary to intrinsic disorders of the RBC or to extrinsic causes. In the congenital hemolytic anemias, intrinsic RBC enzyme, RBC membrane, and hemoglobin disorders result in hemolysis. The typical clinical presentation is a patient with pallor, anemia, jaundice, and often splenomegaly. The laboratory features include anemia, hyperbilirubinemia, and reticulocytosis. For some congenital hemolytic anemias, splenectomy is curative. However, in other diseases, avoidance of drugs and toxins is the best therapy. Supportive care with transfusions are also mainstays of therapy. Chronic hemolysis often results in the formation of gallstones, and cholecystectomy is often indicated.

  9. Homozygosity mapping of Fanconi anemia

    SciTech Connect

    Gschwend, M.; Botstein, D.; Kruglyak, L.

    1994-09-01

    Fanconi anemia (FA) is a rare, recessive, genetically heterogeneous disease characterized by progressive insufficiency of the bone marrow and increased cellular sensitivity to DNA crosslinking agents. Complementation tests among different FA cells have indicated the presence of at least 4 FA-causing genes. One of the genes, FACC, was identified by functional complementation but appears unlikely to account for many phenotypically indistinguishable FA caes. We have begun a linkage study of FA using {open_quotes}homozygosity mapping{close_quotes}, a method that involves genotyping with DNA markers on affected individuals whose parents are related. Because FA is a rare recessive disease, it is most likely that probands are homozygous by descent at the disease locus and, therefore, at nearby DNA markers. Although the probability that any given marker will be homozygous in an inbred individual is high, given markers with moderate heterozygosities, the chance that two unrelated inbred individuals will be homozygous at the same marker is considerably lower. By locating overlapping regions of homozygosity between different families we hope to identify genes that cause FA. Sixteen consanguineous non-FACC FA families from the International Fanconi Anemia Registry at Rockefeller University are under study. An efficient algorithm for data analysis was developed and incorporated into software that can quickly compute exact multipoint lod scores using all markers on an entire chromosome. At the time of this writing, 171 of 229 microsatellite markers spaced at 20 cM intervals across the genome have been analyzed.

  10. Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35

    SciTech Connect

    Abdalla, J.A.; Casley, W.L.; Cousin, H.K.; Hudson, A.J.; Hashimoto, L.; Ebers, G.C. ); Murphy, E.G. ); Cornelis, F.C. )

    1992-09-01

    The chromosomal localization of the gene for Thomsen disease, an autosomal dominant form of myotonia congenita, is unknown. Electrophysiologic data in Thomsen disease point to defects in muscle-membrane ion-channel function. A mouse model of myotonia congenita appears to result from transposon inactivation of a muscle chloride-channel gene which maps to a region of mouse chromosome 6. The linkage group containing this gene includes several loci which have human homologues on human chromosome 7q31-35 (synteny), and this is a candidate region for the Thomsen disease locus. Linkage analysis of Thomsen disease to the T-cell-receptor beta (TCRB) locus at 7q35 was carried out in four pedigrees (25 affected and 23 unaffected individuals) by using a PCR-based dinucleotide repeat polymorphism in the TCRB gene. Two-point linkage analysis between Thomsen disease and TCRB showed a maximum cumulative lod score of 3.963 at a recombination fraction of .10 (1-lod support interval .048-.275). The authors conclude that the Thomsen disease locus is linked to the TCRB locus in these families. 30 refs., 6 figs., 1 tab.

  11. [Refractory anemias].

    PubMed

    Efira, A; Azerad, M-A

    2013-09-01

    Refractory anemia, also known as myelodysplastic syndromes, forms a group of clonal diseases characterized by cytopenias with mostly rich bone marrow. Preferentially reaching an older population, the prognosis depends on both comorbidities and characteristics of the disease, which have been grouped into a score established in 1997 ("IPSS = International Prognostic Scoring System") and revised in 2012 ("R-IPSS = Revised IPSS"). Overall survival and risk of transformation into acute nonlymphoblastic leukemia can now be estimated fairly accurately. Based on these characteristics, the treatment will be mainly supportive or will use several new molecules: growth factors, lenalidomide, 5-azacitidine, etc. A minority of patients may also benefit from allogeneic BMT or sometimes immunosuppressive therapy.

  12. Hemoglobin C, S-C, and E Diseases

    MedlinePlus

    ... Hemolytic Anemia Hemoglobin C, S-C, and E Diseases Iron Deficiency Anemia Sickle Cell Disease Thalassemias Vitamin Deficiency Anemia ( ... Hemolytic Anemia Hemoglobin C, S-C, and E Diseases Iron Deficiency Anemia Sickle Cell Disease Thalassemias Vitamin Deficiency Anemia ...

  13. The epidemiology of anemia in pediatric inflammatory bowel disease: prevalence and associated factors at diagnosis and follow-up and the impact of exclusive enteral nutrition.

    PubMed

    Gerasimidis, Konstantinos; Barclay, Andrew; Papangelou, Alexandros; Missiou, Despoina; Buchanan, Elaine; Tracey, Cardigan; Tayler, Rachel; Russell, Richard K; Edwards, Christine A; McGrogan, Paraic

    2013-10-01

    Anemia is poorly studied in pediatric inflammatory bowel disease. This study explored the epidemiology and associated factors of anemia at diagnosis, after 1 year, and during treatment with exclusive enteral nutrition (EEN). Three cohorts were included: (1) a representative population of newly diagnosed inflammatory bowel disease children (n = 184); (2) patients currently receiving care with data available at diagnosis (n = 179) and after 1 year (n = 139); and (3) 84 children treated with EEN. At diagnosis, 72% were anemic. Abnormal inflammatory markers were more common in Crohn's disease with severe anemia (severe versus no anemia [%]: raised C-reactive protein; 89% versus 48%; suboptimal albumin; 97% versus 29%; P < 0.002). Anemic children with Crohn's disease had shorter diagnosis delay and lower BMI than nonanemic patients (severe versus mild versus no anemia, median [interquartile range]; diagnosis delay [months]: 3 [3.9] versus 6 [10] versus 8 [18], P < 0.001; BMI z score [SD]: -1.4 [1.4] versus -1.3 [1.5] versus -0.2 [1.4], P = 0.003). Extensive colitis was associated with severe anemia in ulcerative colitis. The proportion of severely anemic patients decreased from 34% to 9% and mild anemia doubled at 1 year. After EEN, severe anemia decreased (32% to 9%; P < 0.001) and the hemoglobin concentration increased by 0.75 g/dL. This was observed only after 8 weeks of treatment. Disease improvement and low hemoglobin at EEN initiation but not weight gain were associated with hemoglobin improvement. Anemia is high at diagnosis and follow-up and should receive more attention from the clinical team; however, the focus should remain suppression of inflammatory process in active disease.

  14. Fine mapping of the 9q31 Hirschsprung’s disease locus

    PubMed Central

    Tang, C. S.; Sribudiani, Y.; Miao, X. P.; de Vries, A. R.; Burzynski, G.; So, M. T.; Leon, Y. Y.; Yip, B. H.; Osinga, J.; Hui, K. J. W. S.; Verheij, J. B. G. M.; Cherny, S. S.; Tam, P. K. H.; Sham, P. C.

    2010-01-01

    Hirschsprung’s disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 × 10−6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCR-association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. Electronic supplementary material The online version of this article (doi:10.1007/s00439-010-0813-8) contains supplementary material, which is available to authorized users. PMID:20361209

  15. PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease.

    PubMed

    Beecham, Gary W; Dickson, Dennis W; Scott, William K; Martin, Eden R; Schellenberg, Gerard; Nuytemans, Karen; Larson, Eric B; Buxbaum, Joseph D; Trojanowski, John Q; Van Deerlin, Vivianna M; Hurtig, Howard I; Mash, Deborah C; Beach, Thomas G; Troncoso, Juan C; Pletnikova, Olga; Frosch, Matthew P; Ghetti, Bernardino; Foroud, Tatiana M; Honig, Lawrence S; Marder, Karen; Vonsattel, Jean Paul; Goldman, Samuel M; Vinters, Harry V; Ross, Owen A; Wszolek, Zbigniew K; Wang, Liyong; Dykxhoorn, Derek M; Pericak-Vance, Margaret A; Montine, Thomas J; Leverenz, James B; Dawson, Ted M; Vance, Jeffery M

    2015-03-10

    To minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls. Four hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis. A small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.2 × 10(-8)). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1. We confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD. © 2015 American Academy of Neurology.

  16. Identification of a Hashimoto thyroiditis susceptibility locus via a genome-wide comparison with Graves' disease.

    PubMed

    Oryoji, Daisuke; Ueda, Sho; Yamamoto, Ken; Yoshimura Noh, Jaeduk; Okamura, Ken; Noda, Mitsuhiko; Watanabe, Natsuko; Yoshihara, Ai; Ito, Koichi; Sasazuki, Takehiko

    2015-02-01

    Hashimoto thyroiditis (HT) and Graves' disease (GD) share some immunological features. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these two related diseases. The aim of this study was to identify a non-HLA susceptibility locus that is specific to either HT or GD. We performed a two-stage genome-wide comparison between HT and GD in Japan. During the discovery stage, we performed a logistic regression analysis adjusting for sex using 727 413 single nucleotide polymorphisms (SNPs) for 265 HT and 261 GD patients. During the replication stage, 35 SNPs were analyzed for 181 HT and 286 GD cases. A combined meta-analysis was performed using the results from these two stages. An SNP showing a genome-wide significant level was further analyzed using 1363 healthy controls to determine the specificity of susceptibility. A genome-wide direct comparison between HT and GD revealed an SNP at the VAV3 locus with genome-wide significant association signals (rs7537605: P(combined) = 3.90 × 10(-8); odds ratio(combined) = 1.77; 95% confidence interval = 1.44-2.17). An association analysis using healthy controls showed that rs7537605 is significantly associated with HT (P = 1.24 × 10(-5); odds ratio = 1.60; 95% confidence interval = 1.30-1.97) but not with GD (P = .50), suggesting that the variant specifically affects susceptibility to HT. A genome-wide direct comparison between HT and GD revealed an HT-specific variant within VAV3 in the Japanese. Considering physiological roles of VAV3, such as a guanine nucleotide exchange factor, our finding provides new insight into the molecular mechanism of HT.

  17. PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease

    PubMed Central

    Beecham, Gary W.; Dickson, Dennis W.; Scott, William K.; Martin, Eden R.; Schellenberg, Gerard; Nuytemans, Karen; Larson, Eric B.; Buxbaum, Joseph D.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Hurtig, Howard I.; Mash, Deborah C.; Beach, Thomas G.; Troncoso, Juan C.; Pletnikova, Olga; Frosch, Matthew P.; Ghetti, Bernardino; Foroud, Tatiana M.; Honig, Lawrence S.; Marder, Karen; Vonsattel, Jean Paul; Goldman, Samuel M.; Vinters, Harry V.; Ross, Owen A.; Wszolek, Zbigniew K.; Wang, Liyong; Dykxhoorn, Derek M.; Pericak-Vance, Margaret A.; Montine, Thomas J.; Leverenz, James B.; Dawson, Ted M.

    2015-01-01

    Objective: To minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls. Methods: Four hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis. Results: A small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.2 × 10−8). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1. Conclusions: We confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD. PMID:25663231

  18. High Dose Cyclophosphamide without Stem Cell Rescue in 207 Patients with Aplastic anemia and other Autoimmune Diseases

    PubMed Central

    DeZern, Amy E.; Petri, Michelle; Drachman, Daniel B.; Kerr, Doug; Hammond, Edward R.; Kowalski, Jeanne; Tsai, Hua-Ling; Loeb, David M.; Anhalt, Grant; Wigley, Fredrick; Jones, Richard J.; Brodsky, Robert A.

    2011-01-01

    High-dose cyclophosphamide has long been used an anticancer agent, a conditioning regimen for hematopoietic stem cell transplantation and as potent immunosuppressive agent in autoimmune diseases including aplastic anemia. High-dose cyclophosphamide is highly toxic to lymphocytes but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase, the major mechanism of cyclophosphamide inactivation. High dose cyclophosphamide therapy induces durable remissions in most patients with acquired aplastic anemia. Moreover, high-dose cyclophosphamide without hematopoietic stem cell rescue has shown activity in a variety of other severe autoimmune diseases. Here we review the history of cyclophosphamide as is applies to aplastic anemia (AA) and other autoimmune diseases. Included here are the historical data from early patients treated for AA as well as an observational retrospective study in a single tertiary care hospital. This latter component was designed to assess the safety and efficacy of high-dose cyclophosphamide therapy without stem cell rescue in patients with refractory autoimmune diseases. We analyzed fully the 140 patients with severe, progressive autoimmune diseases treated. All patients discussed here received cyclophosphamide, 50 mg/kg per day for 4 consecutive days. Response, relapse and overall survival were measured. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose of, or administration of new, immunosuppressive medications. Hematologic recovery occurred in all patients. The overall response rate of the was 95%, and 44% of those patients remain progression-free with a median follow up time of 36 (range 1–120) months for the 140 patients analyzed together. The overall actuarial and event free survival across all diseases at 60 months is 90.7% and 20

  19. Evidence for a mouse pathogenicity locus in certain temperature-sensitive mutants of foot-and-mouth disease virus.

    PubMed Central

    Richmond, J Y

    1977-01-01

    Serial tissue culture passaging of three foot-and-mouth disease temperature-sensitive mutants demonstrated the stability of their temperature sensitivity and mouse avirulence characteristics. Recovery of mouse-virulent temperature-sensitive viruses after passage of the mutants in mice suggested that these were not covariant expressions of the same locus, but were under the control of different genes. PMID:197007

  20. Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

    USDA-ARS?s Scientific Manuscript database

    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

  1. Information Needs of Cancer Patients and Perception of Impact of the Disease, of Self-Efficacy, and Locus of Control.

    PubMed

    Keinki, C; Seilacher, E; Ebel, M; Ruetters, D; Kessler, I; Stellamanns, J; Rudolph, I; Huebner, J

    2016-09-01

    The aim of our study was to investigate the relationship between information needs and cancer patients' perceptions of the impact of the disease, self-efficacy, and locus of control. Using a standardized questionnaire, we obtained data from patients who attended a series of lectures. The questionnaire included questions on their information needs, sources of information, satisfaction with information, and short questionnaires on self-efficacy, perception of the disease, and locus of control of reinforcement. Data was obtained from 185 patients. Our results showed that the sources of information that were most often used were physicians (84 %), print media (68 %), and the Internet (59 %); online fora (7.5 %), non-medical practitioners (9.7 %), and telephone-based counseling (8.6 %) were only used by a minority. Patients with a high perception of their own control over the disease more often used any source of information available to them and were more often interested in acquiring additional information. Higher self-efficacy was significantly associated with the need for information on all topics. Patients with a higher external locus of control significantly more often used sources of information and had significantly more need for additional information. By contrast, there were no associations with an internal locus of control. Neither external nor internal locus of control showed any associations with satisfaction with information. Information needs seem to be higher in patients with a high external locus of control and low self-efficacy. Physicians, other professionals, and institutions that provide information may take these relationships into consideration for tailoring their services to patients.

  2. PoCos: Population Covering Locus Sets for Risk Assessment in Complex Diseases

    PubMed Central

    Koyutürk, Mehmet

    2016-01-01

    Susceptibility loci identified by GWAS generally account for a limited fraction of heritability. Predictive models based on identified loci also have modest success in risk assessment and therefore are of limited practical use. Many methods have been developed to overcome these limitations by incorporating prior biological knowledge. However, most of the information utilized by these methods is at the level of genes, limiting analyses to variants that are in or proximate to coding regions. We propose a new method that integrates protein protein interaction (PPI) as well as expression quantitative trait loci (eQTL) data to identify sets of functionally related loci that are collectively associated with a trait of interest. We call such sets of loci “population covering locus sets” (PoCos). The contributions of the proposed approach are three-fold: 1) We consider all possible genotype models for each locus, thereby enabling identification of combinatorial relationships between multiple loci. 2) We develop a framework for the integration of PPI and eQTL into a heterogenous network model, enabling efficient identification of functionally related variants that are associated with the disease. 3) We develop a novel method to integrate the genotypes of multiple loci in a PoCo into a representative genotype to be used in risk assessment. We test the proposed framework in the context of risk assessment for seven complex diseases, type 1 diabetes (T1D), type 2 diabetes (T2D), psoriasis (PS), bipolar disorder (BD), coronary artery disease (CAD), hypertension (HT), and multiple sclerosis (MS). Our results show that the proposed method significantly outperforms individual variant based risk assessment models as well as the state-of-the-art polygenic score. We also show that incorporation of eQTL data improves the performance of identified POCOs in risk assessment. We also assess the biological relevance of PoCos for three diseases that have similar biological mechanisms and

  3. Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia.

    PubMed

    Hershko, Chaim; Hoffbrand, A Victor; Keret, Dan; Souroujon, Moshe; Maschler, Itzhak; Monselise, Yehudit; Lahad, Amnon

    2005-05-01

    Conventional endoscopic and radiographic methods fail to identify a probable source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients, as well as subjects refractory to oral iron treatment, are often referred for hematologic evaluation. Patient clinic, screened for non-bleeding gastrointestinal conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H. pylori infection (IgG antibodies confirmed by urease breath test). The mean age of all subjects was 39+/-18 years, and 119 of 150 were females. We identified 8 new cases of adult celiac disease (5%). Forty IDA patients (27%) had autoimmune atrophic gastritis of whom 22 had low serum vitamin B12 levels. H. pylori infection was the only finding in 29 patients (19%), but was a common co-existing finding in 77 (51%) of the entire group. Refractoriness to oral iron treatment was found in 100% of patients with celiac disease, 71% with autoimmune atrophic gastritis, 68% with H. pylori infection, but only 11% of subjects with no detected underlying abnormality. H. pylori eradication in previously refractory IDA patients in combination with continued oral iron therapy resulted in a significant increase in hemoglobin from 9.4+/-1.5 (mean +/- 1SD) before, to 13.5+/-1.2 g/ dL (p<0.001 by paired t test) within 3 to 6 months. The recognition that autoimmune atrophic gastritis and H. pylori infection may have a significant role in the development of unexplained or refractory IDA in a high proportion of patients should have a strong impact on our daily practice of diagnosing and managing IDA.

  4. Nutritional anemias.

    PubMed

    Hoffbrand, A V; Herbert, V

    1999-10-01

    Folate, vitamin B12, and iron are the subjects of active biochemical and molecular research so that further understanding of their metabolism in health and in a wide variety of Inherited and acquired diseases can be achieved. The roles of folate and vitamin B12 in cardiovascular and neurologic diseases and in neural tube defects (NTDs) will be further explored in the next decade. The effects of prophylactic therapy and of food fortification with the vitamins on these diseases remain to be established. Iron deficiency is a public health problem in all countries and prevention or treatment, particularly in children in developing countries, are major goals. The increased recent understanding of iron metabolism and absorption may clarify the etiology of diseases of iron metabolism and of dietary iron overload. Improved iron chelation therapy for transfusion-dependent patients with refractory anemias will continue to be actively researched over the next decades.

  5. Oral manifestations compatible with chronic graft-versus-host disease in patients with Fanconi anemia.

    PubMed

    Grein Cavalcanti, Laura; Fuentes Araújo, Renata L; Bonfim, Carmem; Torres-Pereira, Cassius C

    2015-02-01

    Fanconi anemia (FA) is a genetic disease that is characterized by several congenital abnormalities and progressive bone marrow failure and is associated with an increased susceptibility to malignant disorders. Currently, the only potential cure for hematological disorders is hematopoietic stem cell transplantation (HSCT). However, 1 of the most common complications after HSCT is the development of oral chronic graft-versus-host disease (cGVHD), which is also a risk factor for the development of cancer, particularly oral squamous cell carcinoma. Therefore, the purpose of this study was to describe the prevalence and characteristics of oral manifestations compatible with cGVHD in patients diagnosed with FA according to the National Institutes of Health (NIH) consensus criteria. A total of 96 patients (51 females, 45 males; median age, 16 years) with FA, who were in medical follow-up after HSCT at the outpatient clinic of the bone marrow transplantation unit (Hospital de Clínicas from the Universidade Federal do Paraná) underwent an oral evaluation between January 2013 and December 2013. Post-HSCT periods varied from 1 to 261 months and were divided into 3 periods: immediate post-HSCT period; intermediate post-HSC period, and late post-HSCT period. Among the evaluated patients, 40 of 96 (42%) presented with oral manifestations of cGVHD, with 29 of 40 (73%) of these patients in the late post-HSCT period. NIH scale scores varied from 0 to 10, and lichenoid and hyperkeratotic lesions were the abnormalities most frequently observed (100%). Overall, a high prevalence of oral manifestations was observed for cGVHD patients with FA. These data highlight the importance of monitoring oral manifestations compatible with cGVHD to identify and treat individuals with a higher risk of developing oral cancer. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Effects of chicken anemia virus and infectious bursal disease virus in commercial chickens.

    PubMed

    Toro, H; van Santen, V L; Hoerr, F J; Breedlove, C

    2009-03-01

    The effects of chicken anemia virus (CAV) and infectious bursal disease virus (IBDV) coinfection in commercial layer-type and meat-type (broiler) chickens with specific maternal immunity were evaluated. In addition, the broiler progeny used had been vaccinated in ovo against IBDV. Layer chickens were inoculated intramuscularly on day 3 of age with CAV and orally on day 7 of age with an IBDV standard strain (APHIS). Broiler chickens were exposed to CAV and/or an IBDV variant strain (AL2) via the drinking water on days 3 and 14 of age. Following CAV and IBDV inoculation neither mortality nor overt clinical disease was observed in any layer or broiler group. In spite of maternal immunity against both IBDV and CAV, mean hematocrits of all layer groups inoculated with CAV (CAV, CAV + APHIS) were lower than uninfected chickens. IBDV APHIS alone or in combination with CAV did not affect the layer weight gain. However, on day 30 of age and concomitantly with maternal antibody decay, bursa lymphocyte depletion became evident in CAV + APHIS-infected layer chickens. These birds (CAV + APHIS) also seroconverted to IBDV on day 35 of age. CAV persisted at low levels in the layer chickens throughout the experimental period in CAV- and CAV+APHIS-infected chickens. Similarly, infected broiler chickens did not show changes in weight gain. Compared to CAV-infected or uninfected controls, CAV+AL2- and AL2-infected broiler chickens showed significant lymphocyte depletion in the bursa as assessed both by bursal indices and histomorphometry. Broilers also seroconverted to IBDV after day 30 of age confirming that bursal lymphocyte depletion was due to IBDV resuming replication. Thymus histomorphometry revealed significant lymphocyte depletion in all infected broiler groups at 30 days of age, but only in CAV+AL2-infected broiler chickens at 41 days of age, suggesting that IBDV infection delayed repopulation of the thymus.

  7. Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease.

    PubMed Central

    Tutois, S; Montagutelli, X; Da Silva, V; Jouault, H; Rouyer-Fessard, P; Leroy-Viard, K; Guénet, J L; Nordmann, Y; Beuzard, Y; Deybach, J C

    1991-01-01

    A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. Images PMID:1939658

  8. Neonatal anemia.

    PubMed

    Aher, Sanjay; Malwatkar, Kedar; Kadam, Sandeep

    2008-08-01

    Neonatal anemia and the need for red blood cell (RBC) transfusions are very common in neonatal intensive care units. Neonatal anemia can be due to blood loss, decreased RBC production, or increased destruction of erythrocytes. Physiologic anemia of the newborn and anemia of prematurity are the two most common causes of anemia in neonates. Phlebotomy losses result in much of the anemia seen in extremely low birthweight infants (ELBW). Accepting a lower threshold level for transfusion in ELBW infants can prevent these infants being exposed to multiple donors.

  9. Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease

    PubMed Central

    Hampe, J; Lynch, N; Daniels, S; Bridger, S; Macpherson, A; Stokkers, P; Forbes, A; Lennard-Jones, J; Mathew, C; Curran, M; Schreiber, S

    2001-01-01

    BACKGROUND AND AIMS—Genetic predisposition for inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic linkage studies. Genetic linkage of IBD to chromosome 3 has been observed previously. A high density analysis of chromosome 3p was performed to confirm prior linkages and elucidate potential genetic associations.
METHODS—Forty three microsatellite markers on chromosome 3 were genotyped in 353 affected sibling pairs of North European Caucasian extraction (average marker density 2 cM in the linkage interval). Marker order was defined by genetic and radiation hybrid techniques.
RESULTS—The maximum single point logarithm of odds (LOD) score was observed for Crohn's disease at D3S3591. Peak multipoint LOD scores of 1.65 and 1.40 for the IBD phenotype were observed near D3S1304 (distal 3p) and near D3S1283 in the linkage region previously reported. Crohn's disease contributed predominantly to the linkage. The transmission disequilibrium test showed significant evidence of association (p=0.009) between allele 4 of D3S1076 and the IBD phenotype (51 transmitted v 28 non-transmitted). Two known polymorphisms in the CCR2 and CCR5 genes were analysed, neither of which showed significant association with IBD. Additional haplotype associations were observed in the vicinity of D3S1076.
CONCLUSIONS—This study provides confirmatory linkage evidence for an IBD susceptibility locus on chromosome 3p and suggests that CCR2 and CCR5 are unlikely to be major susceptibility loci for IBD. The association findings in this region warrant further investigation.


Keywords: inflammatory bowel disease; fine mapping; chromosome 3 PMID:11156639

  10. Prevalence and determinants of anemia in adults with complex congenital heart disease and ventricular dysfunction (subaortic right ventricle and single ventricle physiology).

    PubMed

    Collins, Nicholas; Piran, Sanaz; Harrison, Jeanine; Azevedo, Eduardo; Oechslin, Erwin; Silversides, Candice K

    2008-09-01

    Anemia is well recognized as a marker of poor prognosis in patients with acquired heart disease and heart failure. Adults with complex congenital heart disease and ventricular dysfunction (subaortic right ventricle or single-ventricle physiology) represent a different population, because they are typically much younger and have less co-morbidity compared with patients with acquired forms of heart disease. The purpose of this study was to evaluate the prevalence and determinants of anemia in this population. Baseline hemoglobin levels were recorded at the time of the initial clinic visit, and final hemoglobin levels were those recorded before death or transplantation or at study completion. Anemia was defined as hemoglobin <135 g/L in men and <120 g/L in women. One hundred sixty-seven patients (100 men, mean age 34 +/- 8 years, mean ejection fraction 35 +/- 9%) were included, 66 with atrial switch operations, 42 with congenitally corrected transposition of the great arteries, and 59 with Fontan physiology. The mean hemoglobin level at baseline was 149 +/- 22 g/L and at follow-up was 139 +/- 29 g/L. The overall prevalence of anemia was 29% at completion. Hyponatremia, decreased renal function, and the use of warfarin were independent predictors of anemia. In conclusion, anemia is common in patients with complex congenital heart disease and ventricular dysfunction, in particular those with Fontan physiology.

  11. Quantitative trait locus analysis of fungal disease resistance factors on a molecular map of grapevine.

    PubMed

    Fischer, B M; Salakhutdinov, I; Akkurt, M; Eibach, R; Edwards, K J; Töpfer, R; Zyprian, E M

    2004-02-01

    A full-sibling F1 population comprising 153 individuals from the cross of 'Regent' x 'Lemberger' was employed to construct a genetic map based on 429 molecular markers. The newly-bred red grapevine variety 'Regent' has multiple field-resistance to fungal diseases inherited as polygenic traits, while 'Lemberger' is a traditional fungus-susceptible cultivar. The progeny segregate quantitatively for resistances to Plasmopara viticola and Uncinula necator, fungal pathogens that threaten viticulture in temperate areas. A double pseudo-testcross strategy was employed to construct the two parental maps under high statistical stringency for linkage to obtain a robust marker frame for subsequent quantitative trait locus (QTL) analysis. In total, 185 amplified fragment length polymorphism, 137 random amplified polymorphic DNA, 85 single sequence repeat and 22 sequence characterized amplified region or cleaved amplified polymorphic sequence markers were mapped. The maps were aligned by co-dominant or doubly heterozygous dominant anchor markers. Twelve pairs of homologous linkage groups could be integrated into consensus linkage groups. Resistance phenotypes and segregating characteristics were scored as quantitative traits in three or four growing seasons. Interval mapping reproducibly localized genetic factors that correlated with fungal disease resistances to specific regions on three linkage groups of the maternal 'Regent' map. A QTL for resistance to Uncinula necator was identified on linkage group 16, and QTLs for endurance to Plasmopara viticola on linkage groups 9 and 10 of 'Regent'. Additional QTLs for the onset of berry ripening ("veraison"), berry size and axillary shoot growth were identified. Berry color segregated as a simple trait in this cross of two red varieties and was mapped as a morphological marker. Six markers derived from functional genes could be localized. This dissection of polygenic fungus disease resistance in grapevine allows the development of

  12. Lesions in the thymus and bone marrow in chicks with experimentally induced chicken infectious anemia disease

    PubMed Central

    Kuscu, Burak

    2008-01-01

    One-day-old SPF chicks were inoculated with the Cux-l strain of chicken infectious anemia virus (CIAV), and the clinical development of disease and its macroscopic and microscopic alterations in the thymus and bone marrow, were observed. Tissue sections of thymus and bone marrow were stained using the streptavidin-biotin peroxidase method and examined under light microscope for evaluation of antigenic intensities in tissues. Those findings were then compared with blood parameters and ELISA results obtained through collected sera during sacrifice procedures. We sought to determine: the localization of viral antigens in thymus and bone marrow tissues after inoculation, the correlation between antigen intensities and hematologic, serologic and histopathologic findings, definitive diagnostic criteria using histopathologic and immunoperoxidase methods, and the reliability of these methods in the diagnosis of CIAV infection. For this purpose, 83, one-day-old SPF chicks were used. The birds were divided into experimental (n = 52) and control (n = 26) groups. A virus dose of TCID50 of 100,000/ml was administered intramuscularly to every bird in the experimental group. Based on the results of this study, we have suggested that clinical examination, along with macroscopic and microscopic evaluation of the thymus and bone marrow, maybe undertaken starting from day 7 post-inoculation (PI). ELISA, might be of value, as it might give consistent results starting from day 14 PI. However, the most reliable results were obtained through examination of thymus and bone marrow sections from infected birds stained by immunoperoxidase technique, as early as day 4 PI. PMID:18296884

  13. Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease.

    PubMed

    Jannot, Anne-Sophie; Pelet, Anna; Henrion-Caude, Alexandra; Chaoui, Asma; Masse-Morel, Marine; Arnold, Stacey; Sanlaville, Damien; Ceccherini, Isabella; Borrego, Salud; Hofstra, Robert M W; Munnich, Arnold; Bondurand, Nadège; Chakravarti, Aravinda; Clerget-Darpoux, Françoise; Amiel, Jeanne; Lyonnet, Stanislas

    2013-01-01

    Hirschsprung disease (HSCR) genetics is a paradigm for the study and understanding of multigenic disorders. Association between Down syndrome and HSCR suggests that genetic factors that predispose to HSCR map to chromosome 21. To identify these additional factors, we performed a dose-dependent association study on chromosome 21 in Down syndrome patients with HSCR. Assessing 10,895 SNPs in 26 Caucasian cases and their parents led to identify two associated SNPs (rs2837770 and rs8134673) at chromosome-wide level. Those SNPs, which were located in intron 3 of the DSCAM gene within a 19 kb-linkage disequilibrium block region were in complete association and are consistent with DSCAM expression during enteric nervous system development. We replicated the association of HSCR with this region in an independent sample of 220 non-syndromic HSCR Caucasian patients and their parents. At last, we provide the functional rationale to the involvement of DSCAM by network analysis and assessment of SOX10 regulation. Our results reveal the involvement of DSCAM as a HSCR susceptibility locus, both in Down syndrome and HSCR isolated cases. This study further ascertains the chromosome-scan dose-dependent methodology used herein as a mean to map the genetic bases of other sub-phenotypes both in Down syndrome and other aneuploidies.

  14. Linkage mapping of the primary disease locus for collie eye anomaly.

    PubMed

    Lowe, Jennifer K; Kukekova, Anna V; Kirkness, Ewen F; Langlois, Mariela C; Aguirre, Gustavo D; Acland, Gregory M; Ostrander, Elaine A

    2003-07-01

    Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary cea phenotype, choroidal hypoplasia, segregates as an autosomal recessive trait with nearly 100% penetrance. We further report linkage mapping of the primary cea locus to a 3.9-cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region corresponding to human chromosome 2q35. These results suggest the presence of a developmental regulatory gene important in ocular embryogenesis, with potential implications for other disorders of ocular vascularization.

  15. FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer's disease.

    PubMed

    Paroni, Giulia; Seripa, Davide; Fontana, Andrea; D'Onofrio, Grazia; Gravina, Carolina; Urbano, Maria; Cascavilla, Leandro; Pellegrini, Fabio; Greco, Antonio; Pilotto, Alberto

    2014-01-01

    Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer's disease (AD) patients. Forkhead box O1 (FOXO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD. In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion. A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510-70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups. FOXO1 may influence the clinical response to AChEIs in AD patients.

  16. Nutritional anemias and the elderly.

    PubMed

    Carmel, Ralph

    2008-10-01

    Nutritional anemias are important because they are easily reversed and because their underlying causes, most often unrelated to dietary intake, require individualized assessment. Iron-deficiency anemia (IDA) usually results from iron losses accompanying chronic bleeding, including loss to intestinal parasites, or from gastric disorders or malabsorption in the elderly. Cobalamin-deficiency anemia, the only nutritional anemia with predilection for the elderly, nearly always stems from failure of intrinsic factor (IF)-related absorption. Folate-deficiency anemia, the only nutritional anemia usually caused by poor intake, has nearly disappeared in countries that fortify food with folic acid. Copper-deficiency anemia, which usually results from malabsorptive disorders or from medical or nutritional interventions that provide inadequate copper or excess zinc, is uncommon but increasingly recognized. The prevalences of nutritional anemias, which are not always distinguished from non-anemic deficiency, are uncertain. The mean corpuscular volume (MCV) provides an essential diagnostic tool leading to judicious matching of relevant biochemical changes with relevant anemia. Nutritional anemias usually feature abnormal MCV, whereas the predominant anemias in the aged, especially the anemias of chronic disease/chronic inflammation (ACD/ACI), of renal failure, and of unknown causes, are typically normocytic.

  17. Treatment of anemia in heart failure: potential risks and benefits of intravenous iron therapy in cardiovascular disease.

    PubMed

    Jelani, Qurat-ul-ain; Katz, Stuart D

    2010-01-01

    Iron-deficiency anemia is common in patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a subgroup analysis also suggest that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients.

  18. Treatment of Anemia in Heart Failure: Potential Risks and Benefits of Intravenous Iron Therapy in Cardiovascular Disease

    PubMed Central

    Jelani, Qurat-ul-ain; Katz, Stuart D.

    2010-01-01

    Iron-deficiency anemia is common is patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a sub-group analysis also suggests that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients. PMID:20699672

  19. Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2.

    PubMed

    Pankratz, Nathan; Beecham, Gary W; DeStefano, Anita L; Dawson, Ted M; Doheny, Kimberly F; Factor, Stewart A; Hamza, Taye H; Hung, Albert Y; Hyman, Bradley T; Ivinson, Adrian J; Krainc, Dmitri; Latourelle, Jeanne C; Clark, Lorraine N; Marder, Karen; Martin, Eden R; Mayeux, Richard; Ross, Owen A; Scherzer, Clemens R; Simon, David K; Tanner, Caroline; Vance, Jeffery M; Wszolek, Zbigniew K; Zabetian, Cyrus P; Myers, Richard H; Payami, Haydeh; Scott, William K; Foroud, Tatiana

    2012-03-01

    Genome-wide association (GWAS) methods have identified genes contributing to Parkinson's disease (PD); we sought to identify additional genes associated with PD susceptibility. A 2-stage design was used. First, individual level genotypic data from 5 recent PD GWAS (Discovery Sample: 4,238 PD cases and 4,239 controls) were combined. Following imputation, a logistic regression model was employed in each dataset to test for association with PD susceptibility and results from each dataset were meta-analyzed. Second, 768 single-nucleotide polymorphisms (SNPs) were genotyped in an independent Replication Sample (3,738 cases and 2,111 controls). Genome-wide significance was reached for SNPs in SNCA (rs356165; G: odds ratio [OR]=1.37; p=9.3×10(-21)), MAPT (rs242559; C: OR=0.78; p=1.5×10(-10)), GAK/DGKQ (rs11248051; T: OR=1.35; p=8.2×10(-9)/rs11248060; T: OR=1.35; p=2.0×10(-9)), and the human leukocyte antigen (HLA) region (rs3129882; A: OR=0.83; p=1.2×10(-8)), which were previously reported. The Replication Sample confirmed the associations with SNCA, MAPT, and the HLA region and also with GBA (E326K; OR=1.71; p=5×10(-8) Combined Sample) (N370; OR=3.08; p=7×10(-5) Replication sample). A novel PD susceptibility locus, RIT2, on chromosome 18 (rs12456492; p=5×10(-5) Discovery Sample; p=1.52×10(-7) Replication sample; p=2×10(-10) Combined Sample) was replicated. Conditional analyses within each of the replicated regions identified distinct SNP associations within GBA and SNCA, suggesting that there may be multiple risk alleles within these genes. We identified a novel PD susceptibility locus, RIT2, replicated several previously identified loci, and identified more than 1 risk allele within SNCA and GBA. Copyright © 2012 American Neurological Association.

  20. Meta-analysis of Parkinson disease: Identification of a novel locus, RIT2

    PubMed Central

    Pankratz, Nathan; Beecham, Gary W.; DeStefano, Anita L.; Dawson, Ted M.; Doheny, Kimberly F.; Factor, Stewart A.; Hamza, Taye H.; Hung, Albert Y.; Hyman, Bradley T.; Ivinson, Adrian J.; Krainc, Dmitri; Latourelle, Jeanne C.; Clark, Lorraine N.; Marder, Karen; Martin, Eden R.; Mayeux, Richard; Ross, Owen A.; Scherzer, Clemens R.; Simon, David K.; Tanner, Caroline; Vance, Jeffery M.; Wszolek, Zbigniew K.; Zabetian, Cyrus P.; Myers, Richard H.; Payami, Haydeh; Scott, William K.; Foroud, Tatiana

    2011-01-01

    Objective Genome-wide association (GWAS) methods have identified genes contributing to Parkinson disease (PD); we sought to identify additional genes associated with PD susceptibility. Methods A two stage design was used. First, individual level genotypic data from five recent PD GWAS (Discovery Sample: 4,238 PD cases and 4,239 controls) were combined. Following imputation, a logistic regression model was employed in each dataset to test for association with PD susceptibility and results from each dataset were meta-analyzed. Second, 768 SNPs were genotyped in an independent Replication Sample (3,738 cases and 2,111 controls). Results Genome-wide significance was reached for SNPs in SNCA (rs356165, G: odds ratio (OR)=1.37; p=9.3 × 10−21), MAPT (rs242559, C: OR=0.78; p=1.5 × 10−10), GAK/DGKQ (rs11248051, T:OR=1.35; p=8.2 × 10−9/ rs11248060, T: OR=1.35; p=2.0×10−9), and the HLA region (rs3129882, A: OR=0.83; p=1.2 × 10−8), which were previously reported. The Replication Sample confirmed the associations with SNCA, MAPT, and the HLA region and also with GBA (E326K OR=1.71; p=5 × 10−8 Combined Sample) (N370 OR=3.08; p=7 × 10−5 Replication sample). A novel PD susceptibility locus, RIT2, on chromosome 18 (rs12456492; p=5 × 10−5 Discovery Sample; p=1.52 × 10−7 Replication sample; p=2 × 10−10 Combined Sample) was replicated. Conditional analyses within each of the replicated regions identified distinct SNP associations within GBA and SNCA, suggesting that there may be multiple risk alleles within these genes. Interpretation We identified a novel PD susceptibility locus, RIT2, replicated several previously identified loci, and identified more than one risk allele within SNCA and GBA. PMID:22451204

  1. Pentoxifylline for Anemia in Chronic Kidney Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Bolignano, Davide; D’Arrigo, Graziella; Pisano, Anna; Coppolino, Giuseppe

    2015-01-01

    Background Pentoxifylline (PTX) is a promising therapeutic approach for reducing inflammation and improving anemia associated to various systemic disorders. However, whether this agent may be helpful for anemia management also in CKD patients is still object of debate. Study Design Systematic review and meta-analysis. Population Adults with CKD (any KDOQI stage, including ESKD patients on regular dialysis) and anemia (Hb<13 g/dL in men or < 12 g/dL in women). Search Strategy and Sources Cochrane CENTRAL, EMBASE, Ovid-MEDLINE and PubMed were searched for studies providing data on the effects of PTX on anemia parameters in CKD patients without design or follow-up restriction. Intervention PTX derivatives at any dose regimen. Outcomes Hemoglobin, hematocrit, ESAs dosage and resistance (ERI), iron indexes (ferritin, serum iron, TIBC, transferrin and serum hepcidin) and adverse events. Results We retrieved 11 studies (377 patients) including seven randomized controlled trials (all comparing PTX to placebo or standard therapy) one retrospective case-control study and three prospective uncontrolled studies. Overall, PTX increased hemoglobin in three uncontrolled studies but such improvement was not confirmed in a meta-analysis of seven studies (299 patients) (MD 0.12 g/dL, 95% CI -0.22 to 0.47). Similarly, there were no conclusive effects of PTX on hematocrit, ESAs dose, ferritin and TSAT in pooled analyses. Data on serum iron, ERI, TIBC and hepcidin were based on single studies. No evidence of increased rate of adverse events was also noticed. Limitations Small sample size and limited number of studies. High heterogeneity among studies with respect to CKD and anemia severity, duration of intervention and responsiveness/current therapy with iron or ESAs. Conclusions There is currently no conclusive evidence supporting the utility of pentoxifylline for improving anemia control in CKD patients. Future trials designed on hard, patient-centered outcomes with larger sample

  2. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

    PubMed

    De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

    2017-04-01

    'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

  3. CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation

    PubMed Central

    Reznichenko, Anna; Snieder, Harold; van den Born, Jacob; de Borst, Martin H.; Damman, Jeffrey; van Dijk, Marcory C. R. F.; van Goor, Harry; Hepkema, Bouke G.; Hillebrands, Jan-Luuk; Leuvenink, Henri G. D.; Niesing, Jan; Bakker, Stephan J. L.; Seelen, Marc; Navis, Gerjan

    2012-01-01

    Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys. PMID:22574174

  4. Construction of a yeast artificial chromosome contig encompassing the chromosome 14 Alzheimer`s disease locus

    SciTech Connect

    Sharma, V.; Bonnycastle, L.; Poorkai, P.

    1994-09-01

    We have constructed a yeast artificial chromosome (YAC) contig of chromosome 14q24.3 which encompasses the chromosome 14 Alzheimer`s disease locus (AD3). Determined by linkage analysis of early-onset Alzheimer`s disease kindreds, this interval is bounded by the genetic markers D14S61-D14S63 and spans approximately 15 centimorgans. The contig consists of 29 markers and 74 YACs of which 57 are defined by one or more sequence tagged sites (STSs). The STS markers comprise 5 genes, 16 short tandem repeat polymorphisms and 8 cDNA clones. An additional number of genes, expressed sequence tags and cDNA fragments have been identified and localized to the contig by hybridization and sequence analysis of anonymous clones isolated by cDNA direct selection techniques. A minimal contig of about 15 YACs averaging 0.5-1.5 megabase in length will span this interval and is, at first approximation, in rough agreement with the genetic map. For two regions of the contig, our coverage has relied on L1/THE fingerprint and Alu-PCR hybridization data of YACs provided by CEPH/Genethon. We are currently developing sequence tagged sites from these to confirm the overlaps revealed by the fingerprint data. Among the genes which map to the contig are transforming growth factor beta 3, c-fos, and heat shock protein 2A (HSPA2). C-fos is not a candidate gene for AD3 based on the sequence analysis of affected and unaffected individuals. HSPA2 maps to the proximal edge of the contig and Calmodulin 1, a candidate gene from 4q24.3, maps outside of the region. The YAC contig is a framework physical map from which cosmid or P1 clone contigs can be constructed. As more genes and cDNAs are mapped, a highly resolved transcription map will emerge, a necessary step towards positionally cloning the AD3 gene.

  5. Unraveling Genomic Complexity at a Quantitative Disease Resistance Locus in Maize

    PubMed Central

    Jamann, Tiffany M.; Poland, Jesse A.; Kolkman, Judith M.; Smith, Laurie G.; Nelson, Rebecca J.

    2014-01-01

    Multiple disease resistance has important implications for plant fitness, given the selection pressure that many pathogens exert directly on natural plant populations and indirectly via crop improvement programs. Evidence of a locus conditioning resistance to multiple pathogens was found in bin 1.06 of the maize genome with the allele from inbred line “Tx303” conditioning quantitative resistance to northern leaf blight (NLB) and qualitative resistance to Stewart’s wilt. To dissect the genetic basis of resistance in this region and to refine candidate gene hypotheses, we mapped resistance to the two diseases. Both resistance phenotypes were localized to overlapping regions, with the Stewart’s wilt interval refined to a 95.9-kb segment containing three genes and the NLB interval to a 3.60-Mb segment containing 117 genes. Regions of the introgression showed little to no recombination, suggesting structural differences between the inbred lines Tx303 and “B73,” the parents of the fine-mapping population. We examined copy number variation across the region using next-generation sequencing data, and found large variation in read depth in Tx303 across the region relative to the reference genome of B73. In the fine-mapping region, association mapping for NLB implicated candidate genes, including a putative zinc finger and pan1. We tested mutant alleles and found that pan1 is a susceptibility gene for NLB and Stewart’s wilt. Our data strongly suggest that structural variation plays an important role in resistance conditioned by this region, and pan1, a gene conditioning susceptibility for NLB, may underlie the QTL. PMID:25009146

  6. Identification of a locus controlling Verticillium disease symptom response in Arabidopsis thaliana.

    PubMed

    Veronese, Paola; Narasimhan, Meena L; Stevenson, Rebecca A; Zhu, Jian-K; Weller, Stephen C; Subbarao, Krishna V; Bressan, Ray A

    2003-09-01

    Verticillium dahliae Klebahn is a soil-borne fungal pathogen causing vascular diseases. The pathogen penetrates the host through the roots, spreads through the xylem, and systemically colonizes both resistant and susceptible genotypes. To elucidate the genetic and molecular bases of plant-Verticillium interactions, we have developed a pathosystem utilizing Arabidopsis thaliana and an isolate of V. dahliae pathogenic to both cruciferous and non-cruciferous crops. Relative tolerance (based on symptom severity) but no immunity was found in a survey of Arabidopsis ecotypes. Anthocyanin accumulation, stunting, and chlorosis were common symptoms. Specific responses of the more susceptible ecotype Columbia were induction of early flowering and dying. The more tolerant ecotype C-24 was characterized by pathogen-induced delay of transition to flowering and mild chlorosis symptoms. Genetic analysis indicated that a single dominant locus, Verticillium dahliae-tolerance (VET1), likely functioning also as a negative regulator of the transition to flowering, was able to convey increased tolerance. VET1 was mapped on chromosome IV. The differential symptom responses observed between ecotypes were not correlated with different rates of fungal tissue colonization or with differential transcript accumulation of PR-1 and PDF1.2 defense genes whose activation was not detected during the Arabidopsis-V. dahliae interaction. Impairment in salicylic acid (SA)- or jasmonic acid (JA)-dependent signaling did not cause hypersensitivity to the fungal infection, whereas ethylene insensitivity led to reduced chlorosis and ABA deficiency to reduced anthocyanin accumulation. The results of this study clearly indicated that the ability of V. dahliae to induce disease symptoms is also connected to the genetic control of development and life span in Arabidopsis.

  7. Unraveling genomic complexity at a quantitative disease resistance locus in maize.

    PubMed

    Jamann, Tiffany M; Poland, Jesse A; Kolkman, Judith M; Smith, Laurie G; Nelson, Rebecca J

    2014-09-01

    Multiple disease resistance has important implications for plant fitness, given the selection pressure that many pathogens exert directly on natural plant populations and indirectly via crop improvement programs. Evidence of a locus conditioning resistance to multiple pathogens was found in bin 1.06 of the maize genome with the allele from inbred line "Tx303" conditioning quantitative resistance to northern leaf blight (NLB) and qualitative resistance to Stewart's wilt. To dissect the genetic basis of resistance in this region and to refine candidate gene hypotheses, we mapped resistance to the two diseases. Both resistance phenotypes were localized to overlapping regions, with the Stewart's wilt interval refined to a 95.9-kb segment containing three genes and the NLB interval to a 3.60-Mb segment containing 117 genes. Regions of the introgression showed little to no recombination, suggesting structural differences between the inbred lines Tx303 and "B73," the parents of the fine-mapping population. We examined copy number variation across the region using next-generation sequencing data, and found large variation in read depth in Tx303 across the region relative to the reference genome of B73. In the fine-mapping region, association mapping for NLB implicated candidate genes, including a putative zinc finger and pan1. We tested mutant alleles and found that pan1 is a susceptibility gene for NLB and Stewart's wilt. Our data strongly suggest that structural variation plays an important role in resistance conditioned by this region, and pan1, a gene conditioning susceptibility for NLB, may underlie the QTL.

  8. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    PubMed

    Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S

    2015-01-01

    Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  9. Genome scan in familial late-onset Alzheimer's disease: a locus on chromosome 6 contributes to age-at-onset.

    PubMed

    Zhao, Wei; Marchani, Elizabeth E; Cheung, Charles Y K; Steinbart, Ellen J; Schellenberg, Gerard D; Bird, Thomas D; Wijsman, Ellen M

    2013-03-01

    Alzheimer's disease (AD) is a common, genetically complex, fatal neurodegenerative disorder of late life. Although several genes are known to play a role in early-onset AD, identification of the genetic basis of late onset AD (LOAD) has been challenging, with only the APOE gene known to have a high contribution to both AD risk and age-at-onset. Here, we present the first genome-scan analysis of the complete, well-characterized University of Washington LOAD sample of 119 pedigrees, using age-at-onset as the trait of interest. The analysis approach used allows for a multilocus trait model while at the same time accommodating age censoring, effects of APOE as a known genetic covariate, and full pedigree and marker information. The results provide strong evidence for linkage of loci contributing to age-at-onset to genomic regions on chromosome 6q16.3, and to 19q13.42 in the region of the APOE locus. There was evidence for interaction between APOE and the locus on chromosome 6q and suggestive evidence for linkage to chromosomes 11p13, 15q12-14, and 19p13.12. These results provide the first independent confirmation of an AD age-at-onset locus on chromosome 6 and suggest that further efforts towards identifying the underlying causal locus or loci are warranted.

  10. Abdominal Castleman disease with mixed histopathology in a patient with iron deficiency anemia, growth retardation and peliosis hepatis.

    PubMed

    Saritas, Ulku; Ustundag, Yucel; Isitan, Gokhan; Bastugrul, Settar; Erekul, Selim

    2006-01-01

    In Castleman disease, also known as giant lymph node hyperplasia, lesions are usually located in the chest. Peliosis hepatis is the presence of multiple blood-filled cysts in the liver. The combination of these two disorders in one patient is rare, with only three cases reported to date. We report the case of a 21-year-old man who presented with growth retardation and iron deficiency anemia. Work-up revealed hepatomegaly and multiple conglomerated giant lymph nodes near the splenic hilum. Once the mass was surgically removed, the patient's anemia rapidly resolved and he showed catch-up growth. The lymphoid tissue exhibited mixed histologic type, so the patient was diagnosed with both hyaline vascular type and plasma cell type Castleman disease. A liver biopsy obtained at surgery showed sinusoidal dilatation and blood-filled cysts, indicating peliosis hepatis. This is the fourth documented case of peliosis hepatis associated with Castleman disease. In addition to describing the case features, we discuss the possible pathogenesis of peliosis hepatis in the setting of Castleman disease.

  11. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease.

    PubMed

    Fisher, Sheila A; Tremelling, Mark; Anderson, Carl A; Gwilliam, Rhian; Bumpstead, Suzannah; Prescott, Natalie J; Nimmo, Elaine R; Massey, Dunecan; Berzuini, Carlo; Johnson, Christopher; Barrett, Jeffrey C; Cummings, Fraser R; Drummond, Hazel; Lees, Charlie W; Onnie, Clive M; Hanson, Catherine E; Blaszczyk, Katarzyna; Inouye, Mike; Ewels, Philip; Ravindrarajah, Radhi; Keniry, Andrew; Hunt, Sarah; Carter, Martyn; Watkins, Nick; Ouwehand, Willem; Lewis, Cathryn M; Cardon, Lon; Lobo, Alan; Forbes, Alastair; Sanderson, Jeremy; Jewell, Derek P; Mansfield, John C; Deloukas, Panos; Mathew, Christopher G; Parkes, Miles; Satsangi, Jack

    2008-06-01

    We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.

  12. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn’s disease

    PubMed Central

    Fisher, Sheila A; Tremelling, Mark; Anderson, Carl A; Gwilliam, Rhian; Bumpstead, Suzannah; Prescott, Natalie J; Nimmo, Elaine R; Massey, Dunecan; Berzuini, Carlo; Johnson, Christopher; Barrett, Jeffrey C; Cummings, Fraser R; Drummond, Hazel; Lees, Charlie W; Onnie, Clive M; Hanson, Catherine E; Blaszczyk, Katarzyna; Inouye, Mike; Ewels, Philip; Ravindrarajah, Radhi; Keniry, Andrew; Hunt, Sarah; Carter, Martyn; Watkins, Nick; Ouwehand, Willem; Lewis, Cathryn M; Cardon, Lon; Lobo, Alan; Forbes, Alastair; Sanderson, Jeremy; Jewell, Derek P; Mansfield, John C; Deloukas, Panos; Mathew, Christopher G; Parkes, Miles; Satsangi, Jack

    2009-01-01

    We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn’s disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn’s disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases. PMID:18438406

  13. Feline porphyria associated with anemia, severe hepatic disease, and renal calculi.

    PubMed

    Schnier, Jonathan J; Hanna, Paul

    2010-10-01

    A 13-year-old, neutered male domestic cat presented with signs of weight loss, anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified. Charcoal-like renal calculi and severe liver changes were observed, neither of which has been previously reported in association with feline porphyria.

  14. Feline porphyria associated with anemia, severe hepatic disease, and renal calculi

    PubMed Central

    Schnier, Jonathan J.; Hanna, Paul

    2010-01-01

    A 13-year-old, neutered male domestic cat presented with signs of weight loss, anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified. Charcoal-like renal calculi and severe liver changes were observed, neither of which has been previously reported in association with feline porphyria. PMID:21197209

  15. Severity of Anemia Predicts Hospital Length of Stay but Not Readmission in Patients with Chronic Kidney Disease: A Retrospective Cohort Study.

    PubMed

    Garlo, Katherine; Williams, Deanna; Lucas, Lee; Wong, Rocket; Botler, Joel; Abramson, Stuart; Parker, Mark G

    2015-06-01

    The aim of this study was to examine the relationship of severe anemia to hospital readmission and length of stay (LOS) in patients with chronic kidney disease (CKD) stage 3-5. Compared with the general population, patients with moderate CKD have a higher hospital readmission rate and LOS. Anemia in patients with moderate CKD is associated with higher morbidity and mortality. The influence of anemia on hospital outcomes in patients with moderate CKD has not been characterized.We conducted a retrospective cohort study at Maine Medical Center, a 606-bed academic tertiary care hospital. Patients with CKD stages 3-5 and not on dialysis admitted during February 2013 to January 2014 were eligible. Patients with end stage renal disease on hemodialysis or peritoneal dialysis, kidney transplant, acute kidney injury, gastrointestinal bleeding, active malignancy, pregnancy, and surgery were excluded. The cohort was split into severe anemia (hemoglobin ≤9  g/dL) versus a comparison group (hemoglobin >9 g /dL), and examined for differences in 30-day hospital readmission and LOS.In this study, the data of 1141 patients were included, out of which 156 (13.7%) had severe anemia (mean hemoglobin 8.1 g/dL, SD 0.8). Severe anemia was associated with increased hospital LOS (mean 6.4 (SD 6.0) days vs mean 4.5 (SD 4.0) days, P < 0.001). The difference was 1.7 day longer (95% CI 0.94, 2.45). There was no difference in readmission rate (mean 11.5% vs 10.2%, P = 0.7).Patients with moderate CKD and severe anemia are at risk for increased hospital LOS. Interventions targeting this high-risk population, including outpatient management of anemia, may benefit patient care and save costs through improved hospital outcomes.

  16. Heavy metals in locus ceruleus and motor neurons in motor neuron disease

    PubMed Central

    2013-01-01

    Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

  17. Heavy metals in locus ceruleus and motor neurons in motor neuron disease.

    PubMed

    Pamphlett, Roger; Kum Jew, Stephen

    2013-12-12

    The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons.

  18. Risk of equine infectious anemia virus disease transmission through in vitro embryo production using somatic cell nuclear transfer.

    PubMed

    Gregg, K; Polejaeva, I

    2009-08-01

    Prevention and regulation of equine infectious anemia virus (EIAV) disease transmission solely depend on identification, isolation, and elimination of infected animals because of lack of an effective vaccine. Embryo production via the somatic cell nuclear transfer (SCNT) technology uses oocytes collected mainly from untested animals, which creates a potential risk of EIAV transmission through infected embryos. The current review examines the risk of EIAV disease transmission through SCNT embryo production and transfer. Equine infectious anemia virus is a lentivirus from the family Retroviridae. Because of a lack of direct reports on this subject, relevant information gathered from close relatives of EIAV, such as human immunodeficiency virus (HIV), bovine immunodeficiency virus (BIV), feline immunodeficiency virus (FIV), and small ruminant lentiviruses (SRLVs), is summarized and used to predict the biological plausibility of EIAV disease transmission through transfers of the equine SCNT embryos. Based on published information regarding interaction of oocytes with lentiviruses and the sufficiency of oocyte and embryo washing procedures to prevent lentivirus transmission from in vitro-produced embryos of various species, we predicted the risk of EIAV transmission through SCNT embryo production and transfer to be very small or absent.

  19. Study of anemia in nondialysis dependent chronic kidney disease with special reference to serum hepcidin

    PubMed Central

    Goyal, H.; Mohanty, S.; Sharma, M.; Rani, A.

    2017-01-01

    We studied the role of serum hepcidin in anemia of chronic kidney disease (CKD) in a hospital-based cross-sectional study. Serum hepcidin, ferritin, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated in patients of CKD. Hepcidin levels were increased in patients as compared to healthy adults. Hepcidin levels increased as CKD progressed through stage 3–5 (P trend = 0.015) but did not correlate with estimated glomerular filtration rate. Hepcidin correlated positively with ferritin (P < 0.0001) and transferrin saturation (TSAT) (P = 0.0217) and negatively with erythropoietin (EPO) levels (P = 0.0258) but did not correlate with either hsCRP or estimated glomerular filtration rate. Iron status influenced hepcidin levels of patients. Patients were divided according to iron status on the basis of TSAT and serum ferritin levels. We observed that while absolute iron deficiency (transferrin saturation <20%, ferritin <40 ng/ml) is associated with downregulation of hepcidin, hepcidin is elevated in other two categories of CKD patients (P = 0.0039). Iron status of patients also influenced interaction between hepcidin and hemoglobin (Hb). Hepcidin correlated negatively with Hb in patients with sufficient iron status (r = −0.7452, P < 0.0001) but nearly correlated positively with Hb in patients with absolute iron deficiency (r = 0.9428, P = 0.0572). Almost similar association persisted when cutoff value for serum ferritin was raised to 100 ng/ml as per NKF/KDOQI 2006 clinical practice guidelines except that no association was observed in absolute iron deficiency category. Cutoff value for hepcidin for differentiating absolute iron deficiency from other categories in our study population is ≤ 34 ng/ml (area under curve = 0.836, P < 0.0001). In conclusion, serum hepcidin level is increased in nondialysis CKD patients as compared to healthy adults possibly due to associated inflammation and decreased renal clearance. Furthermore, iron status modifies

  20. Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer`s disease but is not causative

    SciTech Connect

    Bennett, C.; Crawford, F.; Osborne, A.; Diaz, P.

    1995-02-27

    An association has been observed in several independent data sets between late onset Alzheimer`s Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the {epsilon}4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non-stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD. 19 refs., 1 fig., 2 tabs.

  1. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease.

    PubMed

    Fujiwara, Tohru; Ikeda, Takashi; Nagasaka, Yuki; Okitsu, Yoko; Katsuoka, Yuna; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Tomosugi, Naohisa; Harigae, Hideo

    2013-01-01

    Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. The expression of the hepcidin gene, HAMP, is increased in patients with anemia of chronic disease. Previously, the synthetic compound K7174 was identified through chemical screening as a novel inhibitor of the adhesion of monocytes to cytokine-stimulated endothelial cells. K7174 also ameliorated anemia induced by inflammatory cytokines in mice, which suggests a possible involvement of hepcidin regulation. The present study was performed to assess the impact of K7174 on hepcidin expression in a human hematoma cell line and in mice in vivo. We first demonstrated that K7174 treatment in HepG2 cells significantly decreased HAMP expression. Then, we conducted microarray analysis to determine the molecular mechanism by which K7174 inhibits HAMP expression. Transcriptional profiling confirmed the downregulation of HAMP. Surprisingly, we found that K7174 strongly induced GDF15, known as a negative regulator of HAMP expression. Western blotting analysis as well as ELISA confirmed the induction of GDF15 by K7174 treatment. Furthermore, K7174-mediated HAMP suppression was rescued by the silencing of GDF15 expression. Interestingly, we found that K7174 also upregulates CEBPB. Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. Subsequently, we also examined whether K7174 inhibits hepcidin expression in mice. Quantitative RT-PCR analysis with liver samples from K7174-treated mice demonstrated significant upregulation of Gdf15 and downregulation of Hamp expression, as compared to control mice. Furthermore, serum hepcidin concentration was also significantly decreased in K7174-treated mice. In conclusion, K7174 inhibits hepcidin expression partly by inducing GDF15. K-7174 may be a potential therapeutic option to treat anemia of chronic

  2. Hepcidin as a predictive factor and therapeutic target in erythropoiesis-stimulating agent treatment for anemia of chronic disease in rats.

    PubMed

    Theurl, Milan; Nairz, Manfred; Schroll, Andrea; Sonnweber, Thomas; Asshoff, Malte; Haschka, David; Seifert, Markus; Willenbacher, Wolfgang; Wilflingseder, Doris; Posch, Wilfried; Murphy, Anthony T; Witcher, Derrick R; Theurl, Igor; Weiss, Günter

    2014-09-01

    Anemia of chronic disease is a multifactorial disorder, resulting mainly from inflammation-driven reticuloendothelial iron retention, impaired erythropoiesis, and reduced biological activity of erythropoietin. Erythropoiesis-stimulating agents have been used for the treatment of anemia of chronic disease, although with varying response rates and potential adverse effects. Serum concentrations of hepcidin, a key regulator of iron homeostasis, are increased in patients with anemia of chronic disease and linked to the pathogenesis of this disease, because hepcidin blocks cellular iron egress, thus limiting availability of iron for erythropoiesis. We tested whether serum hepcidin levels can predict and affect the therapeutic efficacy of erythropoiesis-stimulating agent treatment using a well-established rat model of anemia of chronic disease. We found that high pre-treatment hepcidin levels correlated with an impaired hematologic response to an erythropoiesis-stimulating agent in rats with anemia of chronic disease. Combined treatment with an erythropoiesis-stimulating agent and an inhibitor of hepcidin expression, LDN-193189, significantly reduced serum hepcidin levels, mobilized iron from tissue stores, increased serum iron levels and improved hemoglobin levels more effectively than did the erythropoiesis-stimulating agent or LDN-193189 monotherapy. In parallel, both the erythropoiesis-stimulating agent and erythropoiesis-stimulating agent/LDN-193189 combined reduced the expression of cytokines known to inhibit erythropoiesis. We conclude that serum hepcidin levels can predict the hematologic responsiveness to erythropoiesis-stimulating agent therapy in anemia of chronic disease. Pharmacological inhibition of hepcidin formation improves the erythropoiesis-stimulating agent's therapeutic efficacy, which may favor a reduction of erythropoiesis-stimulating agent dosages, costs and side effects.

  3. Tracing criteria of successful aging? Health locus of control and well-being in older patients with internal diseases.

    PubMed

    Knappe, Susanne; Pinquart, Martin

    2009-03-01

    To identify differences and similarities in health locus of control (HLC) and well-being between internistic patients, recently diagnosed cancer patients and healthy controls, we examined 110 patients with internal diseases, 196 cancer patients and 80 healthy controls aged 60+ years. HLC was assessed with the Multidimensional Health Locus of Control Scales (MHLC), well-being with the Positive and Negative Affect Schedule. Patients with internal diseases scored highest on internal HLC. Scores on social externalism and fatalism MHCL-subscales of internistic patients were similar to cancer patients. Both patient samples reported reduced positive affect. Higher levels of education, more social support, higher self-esteem, internal HLC and daily functioning predicted positive affect in the total sample. In addition, an interaction effect of internal locus of control and daily functioning was found in cancer patients. There were no group-specific predictors of positive affect. Results suggest that high internal HLC is associated with positive affect in each of the three samples. However, an internal HLC only contributes to positive affect in cancer patients when they are in sufficient physical condition to exert control over their health.

  4. Characterization of a disease susceptibility locus for exploring an efficient way to improve rice resistance against bacterial blight.

    PubMed

    Cheng, Qi; Mao, Weihua; Xie, Wenya; Liu, Qinsong; Cao, Jianbo; Yuan, Meng; Zhang, Qinglu; Li, Xianghua; Wang, Shiping

    2017-03-01

    Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is the most harmful bacterial disease of rice worldwide. Previously, we characterized major disease resistance (MR) gene xa25, which confers race-specific resistance to Xoo strain PXO339. The xa25 is a recessive allele of the SWEET13 locus, but SWEET13's interaction with PXO339 and how efficiently using this locus for rice breeding still need to be defined. Here we show that the SWEET13 allele from rice Zhenshan 97 is a susceptibility gene to PXO339. Using this allele's promoter to regulate xa25 resulted in disease, suggesting that the promoter is a key determinant in SWEET13 caused disease in Zhanshan 97 after PXO339 infection. PXO339 transcriptionally induces SWEET13 to cause disease. Partial suppressing SWEET13 expression leads to a high level of resistance to PXO339. Thus, the transcriptionally suppressed SWEET13 functions as xa25 in resistance to PXO339. Hybrid rice is widely grown in many countries. However, recessive MR genes have not been efficiently used for disease resistance breeding in hybrid rice production for both parents of the hybrid have to carry the same recessive gene. However, the suppressed SWEET13 functions dominantly, which will have advantage to improve the resistance of hybrid rice to xa25-incomptible Xoo.

  5. Linkage Analysis in Autoimmune Addison’s Disease: NFATC1 as a Potential Novel Susceptibility Locus

    PubMed Central

    Mitchell, Anna L.; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U.; Vaidya, Bijay; Erichsen, Martina M.; Darlay, Rebecca; Husebye, Eystein S.; Cordell, Heather J.; Pearce, Simon H. S.

    2015-01-01

    Background Autoimmune Addison’s disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. Methods DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. Results In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. Conclusion This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis. PMID:26042420

  6. Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease.

    PubMed

    Bueno, Clara; Roldan, Mar; Anguita, Eduardo; Romero-Moya, Damia; Martín-Antonio, Beatriz; Rosu-Myles, Michael; del Cañizo, Consuelo; Campos, Francisco; García, Regina; Gómez-Casares, Maite; Fuster, Jose Luis; Jurado, Manuel; Delgado, Mario; Menendez, Pablo

    2014-07-01

    Aplastic anemia is a life-threatening bone marrow failure disorder characterized by peripheral pancytopenia and marrow hypoplasia. The majority of cases of aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency and impaired immune responses are hallmarks underlying the bone marrow failure in this condition. Mesenchymal stem/stromal cells constitute an essential component of the bone marrow hematopoietic microenvironment because of their immunomodulatory properties and their ability to support hematopoiesis, and they have been involved in the pathogenesis of several hematologic malignancies. We investigated whether bone marrow mesenchymal stem cells contribute, directly or indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal stem cell cultures can be established from the bone marrow of aplastic anemia patients and display the same phenotype and differentiation potential as their counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia patients support the in vitro homeostasis and the in vivo repopulating function of CD34(+) cells, and maintain their immunosuppressive and anti-inflammatory properties. These data demonstrate that bone marrow mesenchymal stem cells from patients with aplastic anemia do not have impaired functional and immunological properties, suggesting that they do not contribute to the pathogenesis of the disease.

  7. The co-occurrence of anemia and cardiometabolic disease risk demonstrates sex-specific sociodemographic patterning in an urbanizing rural region of southern India

    PubMed Central

    Jones, Andrew D.; Hayter, Arabella K.M.; Baker, Chris P.; Prabhakaran, Poornima; Gupta, Vipin; Kulkarni, Bharati; Davey Smith, George; Ben-Shlomo, Yoav; Radha Krishna, K.V.; Kumar, P. Uday; Kinra, Sanjay

    2015-01-01

    Background/Objectives To determine the extent and sociodemographic determinants of anemia, overweight, metabolic syndrome (MetS), and the co-occurrence of anemia with cardiometabolic disease risk factors among a cohort of Indian adults. Subject/Methods Cross-sectional survey of adult men (n=3,322) and non-pregnant women (n=2,895) aged 18 y and older from the third wave of the Andhra Pradesh Children and Parents Study that assessed anemia, overweight based on Body Mass Index, and prevalence of MetS based on abdominal obesity, hypertension, and blood lipid and fasting glucose measures. We examined associations of education, wealth and urbanicity with these outcomes and their co-occurrence. Results The prevalence of anemia and overweight was 40% and 29% among women, respectively, and 10% and 25% among men (P<0.001), respectively, while the prevalence of MetS was the same across sexes (15%) (P=0.55). The prevalence of concurrent anemia and overweight (9%), and anemia and MetS (4.5%) was highest among women. Household wealth was positively associated with overweight and MetS across sexes (P<0.05). Independent of household wealth, higher education was positively correlated with MetS among men (OR (95% CI): MetS: 1.4 (0.99, 2.0)) and negatively correlated with MetS among women (MetS: 0.54 (0.29, 0.99)). Similar sex-specific associations were observed for the co-occurrence of anemia with overweight and MetS. Conclusion Women in this region of India may be particularly vulnerable to co-occurring anemia and cardiometabolic risk, and associated adverse health outcomes as the nutrition transition advances in India. PMID:26508461

  8. Genetic homogeneity of Pelizaeus-Merzbacher disease: Tight linkage to the proteolipoprotein locus in 16 affected families

    SciTech Connect

    Boespflug-Tanguy, O.; Mimault, C.; Cavagna, A.; Giraud, G.; Dastugue, B.; Melki, J.; Dinh, D.P.; Dautigny, A.

    1994-09-01

    Among the numerous leukodystrophies that have an early onset and no biochemical markers, Pelizaeus-Merzbacher disease (PMD) is one that can be identified using strict clinical criteria and demonstrating an abnormal formation of myelin that is restricted to the CNS in electrophysiological studies and brain magnetic resonance imaging (MRI). In PMD, 12 different base substitutions and one total deletion of the genomic region containing the PLP gene have been reported, but, despite extensive analysis, PLP exon mutations have been found in only 10%-25% of the families analyzed. To test the genetic homogeneity of this disease, the authors have carried out linkage analysis with polymorphic markers of the PLP genomic region in 16 families selected on strict diagnostic criteria of PMD. They observed a tight linkage of the PMD locus with markers of the PLP gene (cDNA PLP, exon IV polymorphism) and of the Xq22 region (DXS17, DXS94, and DXS287), whereas the markers located more proximally (DXYS1X and DXS3) or distally (DXS11) were not linked to the PMD locus. Multipoint analysis gave a maximal location score for the PMD locus (13.98) and the PLP gene (8.32) in the same interval between DXS94 and DXS287, suggesting that in all families PMD is linked to the PLP locus. Mutations of the extraexonic PLP gene sequences or of another unknown close gene could be involved in PMD. In an attempt to identify molecular defects of this genomic region that are responsible for PMD, these results meant that RFLP analysis could be used to improve genetic counseling for the numerous affected families in which a PLP exon mutation could not be demonstrated. 39 refs., 2 figs., 2 tabs.

  9. Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus

    PubMed Central

    Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M.; Heckman, Michael G.; McCarthy, Allan; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W.; Uitti, Ryan J.; Wszolek, Zbigniew K.; Ross, Owen A.

    2015-01-01

    Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD. PMID:26090850

  10. Thalassemia and sickle cell anemia in Swedish immigrants: Genetic diseases have become global

    PubMed Central

    Hemminki, Kari; Li, Xinjun; Försti, Asta; Sundquist, Jan; Sundquist, Kristina

    2015-01-01

    Aims: Some 15% of the Swedish population is born outside Sweden, originating from all continents of the world. Thalassemia and sickle cell anemia constitute the most common inherited recessive disorders globally and they are endemic in areas of Africa and Asia, origins of many immigrants to Sweden. We aimed at investigating the origins of the Swedish sickle cell and thalassemia patients. Methods: Patients were identified using data from the Swedish Hospital Discharge Register since 1987 and from the Outpatient Register since 2001 up to year 2010. Results: A total of 3064 persons were diagnosed with thalassemia. The incidence was highest, 62.9/100,000 for immigrants from Thailand, followed by Iraqis (47.1/100,000); the rate was 0.7/100,000 among those born in Sweden. The total number of sickle cell anemia patients was 584 and the highest rate of 13.0/100,000 was found for Sub-Saharan immigrants. For thalassemia, 363 of the patients were siblings, while for sickle cell anemia, 180 were siblings. Conclusions: The data showed that >90% of sickle cell and thalassemia patients were first- or second-generation immigrants to Sweden and the endemic regions for these were the origins of immigrants with the highest incidence. Global immigration provides global challenges to national health care systems. PMID:27092253

  11. Thalassemia and sickle cell anemia in Swedish immigrants: Genetic diseases have become global.

    PubMed

    Hemminki, Kari; Li, Xinjun; Försti, Asta; Sundquist, Jan; Sundquist, Kristina

    2015-01-01

    Some 15% of the Swedish population is born outside Sweden, originating from all continents of the world. Thalassemia and sickle cell anemia constitute the most common inherited recessive disorders globally and they are endemic in areas of Africa and Asia, origins of many immigrants to Sweden. We aimed at investigating the origins of the Swedish sickle cell and thalassemia patients. Patients were identified using data from the Swedish Hospital Discharge Register since 1987 and from the Outpatient Register since 2001 up to year 2010. A total of 3064 persons were diagnosed with thalassemia. The incidence was highest, 62.9/100,000 for immigrants from Thailand, followed by Iraqis (47.1/100,000); the rate was 0.7/100,000 among those born in Sweden. The total number of sickle cell anemia patients was 584 and the highest rate of 13.0/100,000 was found for Sub-Saharan immigrants. For thalassemia, 363 of the patients were siblings, while for sickle cell anemia, 180 were siblings. The data showed that >90% of sickle cell and thalassemia patients were first- or second-generation immigrants to Sweden and the endemic regions for these were the origins of immigrants with the highest incidence. Global immigration provides global challenges to national health care systems.

  12. Trends in anemia care in older patients approaching end-stage renal disease in the United States (1995-2010).

    PubMed

    Winkelmayer, Wolfgang C; Mitani, Aya A; Goldstein, Benjamin A; Brookhart, M Alan; Chertow, Glenn M

    2014-05-01

    Anemia is common in patients with advanced chronic kidney disease. Whereas the treatment of anemia in patients with end-stage renal disease (ESRD) has attracted considerable attention, relatively little is known about patterns and trends in the anemia care received by patients before they start maintenance dialysis or undergo preemptive kidney transplantation. To determine the trends in anemia treatment received by Medicare beneficiaries approaching ESRD. Closed cohort study in the United States using national ESRD registry data (US Renal Data System) of patients 67 years or older who initiated maintenance dialysis or underwent preemptive kidney transplantation between 1995 and 2010. All eligible patients had uninterrupted Medicare (A+B) coverage for at least 2 years before ESRD. Time, defined as calendar year of incident ESRD. Use of erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time of ESRD. We used multivariable modified Poisson regression to estimate utilization prevalence ratios (PRs). Records of 466,803 patients were analyzed. The proportion of patients with incident ESRD receiving any ESA in the 2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007; thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR, 9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in 2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010; PR, 9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR, 1.88 [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995, increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9 g/dL in 2010. Between 1995 and 2010, older adults approaching

  13. Understanding the roles of intrinsic disorder in subunits of hemoglobin and the disease process of sickle cell anemia.

    PubMed

    Fitzsimmons, Reis; Amin, Narmin; Uversky, Vladimir N

    2016-01-01

    One of the common genetic disorders is sickle cell anemia, in which 2 recessive alleles must meet to allow for destruction and alteration in the morphology of red blood cells. This usually leads to loss of proper binding of oxygen to hemoglobin and curved, sickle-shaped erythrocytes. The mutation causing this disease occurs in the 6(th) codon of the HBB gene encoding the hemoglobin subunit β (β-globin), a protein, serving as an integral part of the adult hemoglobin A (HbA), which is a heterotetramer of 2 α chains and 2 β chains that is responsible for binding to the oxygen in the blood. This mutation changes a charged glutamic acid to a hydrophobic valine residue and disrupts the tertiary structure and stability of the hemoglobin molecule. Since in the field of protein intrinsic disorder, charged and polar residues are typically considered as disorder promoting, in opposite to the order-promoting non-polar hydrophobic residues, in this study we attempted to answer a question if intrinsic disorder might have a role in the pathogenesis of sickle cell anemia. To this end, several disorder predictors were utilized to evaluate the presence of intrinsically disordered regions in all subunits of human hemoglobin: α, β, δ, ε, ζ, γ1, and γ2. Then, structural analysis was completed by using the SWISS-MODEL Repository to visualize the outputs of the disorder predictors. Finally, Uniprot STRING and D(2)P(2) were used to determine biochemical interactome and protein partners for each hemoglobin subunit along with analyzing their posttranslational modifications. All these properties were used to determine any differences between the 6 different types of subunits of hemoglobin and to correlate the mutation leading to sickle cell anemia with intrinsic disorder propensity.

  14. Anemia and hemoglobin serum levels are associated with exercise capacity and quality of life in chronic obstructive pulmonary disease.

    PubMed

    Ferrari, Marcello; Manea, Lorenzo; Anton, Kamel; Bruzzone, Paola; Meneghello, Mara; Zamboni, Francesco; Purgato, Luigi; Cazzoletti, Lucia; Ferrari, Pietro; Testi, Renato

    2015-05-08

    Little is known about the relationship between hemoglobin concentrations, functional status and health related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD). Our aim was to investigate the prevalence of anemia and the association of hemoglobin with shortness of breath, exercise capacity, muscle strength and HRQL, in COPD patients. A total of 105 COPD patients (77 males, 71.6 ± 9.2 years) were studied. Patients were classified as anemic and non anemic using the WHO criteria. We used the Medical Research Council Dyspnoea scale (MRCs) to measure shortness of breath. Exercise capacity was assessed using the six minute walking distance (6MWD) and the peak of VO2 during the maximal cycle ergometer test (VO2max). We used the Quadriceps and Handgrip strength assessment to determine muscle strength. The Saint George Respiratory Questionnaire was used to investigate HRQL. The physiological/functional characteristics of the two groups were compared. Regression models adjusting for confounders examined the independent association of anemia and of hemoglobin levels with clinical and functional outcomes. Anemic patients (12.3%) showed a significantly higher MRCs, a lower 6MWD, VO2max, and a worse quality of life. On the contrary, there was no difference in muscle strength between the two groups. In the regression models, hemoglobin was independently associated with reduced exercise capacity and HRQL. Anemia in COPD was a risk factor for poorer exercise capacity and quality of life, and these outcomes were linearly associated with hemoglobin. Our results should stimulate further research into exploring whether increasing hemoglobin has a beneficial effect on the outcomes in COPD.

  15. Prevalence of anemia and its impact on mortality in patients with acute exacerbation of chronic obstructive pulmonary disease in a developing country setting.

    PubMed

    Rahimi-Rad, Mohammad Hossein; Sadighi, Tannaz; Rabieepour, Masomeh; Dinparast, Reza; RahimiRad, Shagayegh

    2015-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is going to be the third most common cause of death worldwide. The natural course of COPD is interrupted by acute exacerbations (AECOPD) with an overall mortality rate of 10%. Anemia is a well-known independent predictor of mortality in several chronic diseases. Little is known about the impact of anemia on mortality in AECOPD. The aims of this study were to determine the prevalence of anemia in AECOPD patients and its impact on mortality in a developing country setting. We retrospectively studied 200 hospitalized patients with AECOPD (100 died in hospital and 100 survived) in Imam Khomeini teaching hospital, Urmia, Iran. Prevalence of anemia between deceased and surviving patients compared by using x-square test. Mean admission day Hb and Hct level were compared between the two groups by using Student t-test. Anemia was defined according to WHO criteria: Hb<13 g/dl in males; Hb<12 g/dl in females. The prevalence of anemia was significantly higher in patients who died in hospital compared to those who survived (72% vs. 49%, p=0.001 and OR=2.68). The mean ±SD Hb level was 11.5±2.7 g/dl among deceased patients vs. 13.0±2.0 g/dl among survivors (p value<0.001). The duration of hospitalization was significantly higher (p<0,001) in anemic patients (mean 13.28 days in anemic vs. 7.0 days in non-anemic patients). In bivariate correlation analysis, Hb was positively correlated with FEV1 (r=+0.210, p=0.011) and negatively with duration of hospitalization (r=-0.389, p=0.000). Anemia was common in AECOPD patients in this developing country setting and was significantly associated with in hospital mortality.

  16. Two-locus models of disease: Comparison of likelihood and nonparametric linkage methods

    SciTech Connect

    Goldin, L.R. ); Weeks, D.E. )

    1993-10-01

    The power to detect linkage for likelihood and nonparametric (Haseman-Elston, affected-sib-pair, and affected-pedigree-member) methods is compared for the case of a common, dichotomous trait resulting from the segregation of two loci. Pedigree data for several two-locus epistatic and heterogeneity models have been simulated, with one of the loci linked to a marker locus. Replicate samples of 20 three-generation pedigrees (16 individuals/pedigree) were simulated and then ascertained for having at least 6 affected individuals. The power of linkage detection calculated under the correct two-locus model is only slightly higher than that under a single locus model with reduced penetrance. As expected, the nonparametric linkage methods have somewhat lower power than does the lod-score method, the difference depending on the mode of transmission of the linked locus. Thus, for many pedigree linkage studies, the lod-score method will have the best power. However, this conclusion depends on how many times the lod score will be calculated for a given marker. The Haseman-Elston method would likely be preferable to calculating lod scores under a large number of genetic models (i.e., varying both the mode of transmission and the penetrances), since such an analysis requires an increase in the critical value of the lod criterion. The power of the affected-pedigree-member method is lower than the other methods, which can be shown to be largely due to the fact that marker genotypes for unaffected individuals are not used. 31 refs., 1 fig., 5 tabs.

  17. [Equine Infectious Anemia (EIA)].

    PubMed

    Kaiser, A; Meier, H P; Straub, R; Gerber, V

    2009-04-01

    Equine Infectious Anemia (EIA) is a reportable, eradicable epizootic disease caused by the equine lentivirus of the retrovirus family which affects equids only and occurs worldwide. The virus is transmitted by blood, mainly by sanguivorous insects. The main symptoms of the disease are pyrexia, apathy, loss of body condition and weight, anemia, edema and petechia. However, infected horses can also be inapparent carriers without any overt signs. The disease is diagnosed by serological tests like the Coggins test and ELISA tests. Presently, Switzerland is offi cially free from EIA. However, Switzerland is permanently at risk of introducing the virus as cases of EIA have recently been reported in different European countries.

  18. [Pathophysiology, diagnosis and treatment of anemia].

    PubMed

    Ozawa, Keiya

    2008-03-01

    Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD), thalassemia, megaloblastic anemia, chronic renal failure, hematological malignancies, etc.], excessive RBC destruction [hereditary spherocytosis, inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based on the measured red cell size(MCV), anemia is classified as microcytic, normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.), reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12 level, and Ham test are also useful in the differential diagnosis of anemia. Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed for the treatment of transfusional iron overload is also very useful for the management of patients with bone marrow failure syndromes.

  19. Clinical utility of Beckman-Coulter Gen's reticulocyte analysis in the study of anemia of chronic disease (ACD).

    PubMed

    Rodrigues, Ana; Ortega, Carlos; Santos, Luís; Teixeira, Alexandre; Dinis, Maria Joáo; Vasconcelos, Iponina; Lacerda, Jorge; Fonseca, Elisa

    2007-01-01

    The aim of this study is to analyze the reticulocyte parameters (classical and research parameters) acquired by the Beckman Coulter GEN'S blood counter (GEN'S; Brea, CA, USA) to establish the "reticulocyte profile" characteristics of patients with anemia of chronic disease (ACD). The reticulocyte parameters and profile provided by the GEN'S were studied in 38 anemic patients who fulfilled the diagnostic criteria for the ACD, and the results were compared with those of 38 healthy controls in a multivariate statistical analysis using the Student t-test and the receiver operating characteristics (ROC) curve analysis.Statistically significant (P <.05) differences between the 2 population groups were observed in several of the reticulocyte parameters provided by the GEN'S: mean volume of the reticulocyte population (MRV) (high), percentage of high light scatter reticulocytes HLR% (high), mean volume of the whole sphered red cell and reticulocyte population (MSCV) (high) MCV-MSCV (low) with the highest diagnostic value, as measured by the area under the ROC curve (>0.9), for the IRF (high) and the reticulocyte population data: mean channel scatter retics (high) and the mean channel conductivity retics (high). This study establishes the reticulocyte parameters and reticulocyte profile as provided by the GEN'S and characteristic of patients with ACD as compared with normal subjects. This should provide the basis for further studies comparing the reticulocyte profile of patients with ACD with those found in other types of anemia.

  20. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy.

    PubMed

    Jiang, Yao; Zhang, Jingjing; Yuan, Yanggang; Zha, Xiaoming; Xing, Changying; Shen, Chong; Shen, Zhixiang; Qin, Chao; Zeng, Ming; Yang, Guang; Mao, Huijuan; Zhang, Bo; Yu, Xiangbao; Sun, Bin; Ouyang, Chun; Xu, Xueqiang; Ge, Yifei; Wang, Jing; Zhang, Lina; Cheng, Chen; Yin, Caixia; Zhang, Jing; Chen, Huimin; Ma, Haoyang; Wang, Ningning

    2016-06-16

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m(2). Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.

  1. Artificial intelligence for optimal anemia management in end-stage renal disease.

    PubMed

    Brier, Michael E; Gaweda, Adam E

    2016-08-01

    Computational intelligence for the prediction of hemoglobin to guide the selection of erythropoiesis-stimulating agent dose results in improved anemia management. The models used for the prediction result from the use of individual patient data and help to increase the number of hemoglobin observations within the target range. The benefits of using these modeling techniques appear to be a decrease in erythropoiesis-stimulating agent use and a decrease in the number of transfusions. This study confirms the results of previous smaller studies and suggests that additional beneficial results may be achieved.

  2. Living with Aplastic Anemia

    MedlinePlus

    ... Content: NEXT >> Featured Video Clinical Trials for Rare Blood Diseases (Neal Young, M.D.) 05/17/2012 In ... in the lives of people who have rare blood and bone marrow diseases, such as aplastic anemia. // Non Object? Updated: August ...

  3. Special Education: Aplastic Anemia.

    PubMed

    Teramura; Mizoguchi

    1996-01-01

    WHAT IS HYPOPLASTIC ANEMIA? Aplastic anemia is a hematological disease characterized by pancytopenia and bone marrow hypoplasia. Acquired cases of aplastic anemia are almost all idiopathic and arise from unknown causes. Other cases of aplastic anemia are secondary and are caused by radiation, chemicals or viruses. PATHOPHYSIOLOGY: Aplastic anemia is manifested as a marked reduction in the number of pluripotent hematopoietic stem cells, but why this occurs is still uncertain. Some of the proposed causes include abnormalities of the hematopoietic stem cells, abnormalities in the hematopoietic microenvironment, and immunologically mediated damage to the hematopoietic stem cells (Figure 1). ABNORMALTIES OF THE HEMATOPOIETIC STEM CELLS: Patients with aplastic anemia, and long-term survivors in particular, are at increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute myelocytic leukemia. This suggests that, in at least some of these patients, the hematopoietic stem cells themselves are abnormal. It also suggests that in some of these patients the blood cells are clonal (that is, all the blood cells are derived from a single pluripotent stem cell). In short, what these findings imply is that aplastic anemia may be caused by the emergence of an abnormal clone. Clonal hematopoiesis, however, can also be considered nothing more than a consequence. In other words, it is possible that hematopoiesis in this kind of patient is performed by a lone pluripotent stem cell that somehow managed to survive eradication. No definitive interpretation of clonal hematopoiesis has been agreed upon, and it is still a topic for future research. ABNORMAL HEMATOPOIETIC MICROENVIRONMENT: The presence of stromal cells, which form the microenvironment of bone marrow, is very important in hematopoiesis. Hematopoietic stem cells proliferate and differentiate either by adhering to stromal cells or by being stimulated by the various

  4. Management of renal anemia.

    PubMed

    Peco-Antic, Amira

    2005-01-01

    Normochromic normocytic anemia is common in children with chronic renal failure (CRF) when their glomerular filtration rate is below 35 ml/min/1.73 m2 BSA, but it may develop earlier in some forms of renal disease. An inadequate erythropoiesis due to insufficient erythropoietin synthesis in the kidneys is the main cause of renal anemia. Other reasons include reduced red blood cell lifespan, chronic blood loss, iron deficiency, inhibitors of erythropoiesis, and malnutrition. The presence of anemia contributes to many of the symptoms of uremia, including decreased appetite, decreased energy, poor cardiac function, and poor school performance. Therefore, correction of anemia dramatically improves the life of the child with CRF. Presently, the goal of anemia management is to maintain hematocrit concentrations at 33% to 36% and a hemoglobin concentration of at least 11 g/L. This can be accomplished by intravenous or subcutaneous administration of recombinant erythropoietin (rHuEPO, 100-300 U/kg/week) and iron preparations. If adequate iron stores cannot be maintained with oral therapy (2-3, max 6 mg/kg/day), intravenous iron should be administered. In order to optimize anemia management in children with CRF, future research should be concentrated on the normalization of hemoglobin early in the course of CRF, and the long-term effects on the child's development.

  5. [Heart failure and anemia].

    PubMed

    Reda, S; Motloch, L J; Hoppe, U C

    2013-09-01

    Chronic heart failure has an age-dependent prevalence of 2% and is therefore one of the most frequent diseases in western societies. A reduced hemoglobin concentration according to the definition of the World Health Organization is a common comorbidity affecting more than half of all heart failure patients. Elderly patients, patients suffering from renal impairment and women are more likely to develop anemia but a definitive etiology of anemia is only identified in the minority of cases. Anemia is associated with a poor clinical status and a greater risk of hospitalization and is a predictive factor for increased mortality. The incidence of anemia appears to increase with a poorer functional class. Intravenous iron therapy improves the exercise capacity in patients with systolic heart failure and iron deficiency and is currently being recommended for patients with persistent symptoms despite optimal medical and device therapy. However, erythropoietin-stimulating agents as a treatment for anemia in chronic heart failure have failed to improve clinical outcome in a large randomized trial. In patients with heart failure but with maintained ejection fraction, anemia is also associated with a poor prognosis. Specific therapeutic recommendations for these patients are still not available.

  6. Positive predictive value of the International Classification of Diseases, 10th edition diagnosis codes for anemia caused by bleeding in the Danish National Registry of Patients.

    PubMed

    Zalfani, Jihen; Frøslev, Trine; Olsen, Morten; Ben Ghezala, Inès; Gammelager, Henrik; Arendt, Johan Fb; Erichsen, Rune

    2012-01-01

    Valid data on anemia caused by bleeding are needed for epidemiological research and monitoring health care. The Danish National Registry of Patients (DNRP) is a nationwide medical database with information on all Danish residents' hospital history. We aimed to assess the positive predictive value (PPV) of the diagnostic coding of anemia caused by bleeding in the DNRP. In the DNRP, we identified all patients with International Classification of Disease, 10th edition codes for anemia caused by bleeding (acute: D50.0; chronic: D62.6) at three Danish hospitals from 2000 through 2009. For these patients we computed the PPV using hemoglobin level data, from Aarhus University laboratory database, as reference standard. Anemia was defined by a hemoglobin level less than 7.0 mmol/L for women and less than 8.0 mmol/L for men. We identified 3391 patients in the DNRP with a diagnosis of anemia caused by bleeding. The overall PPV was 95.4% (95% confidence interval [CI]: 94.6%-96.0%). The PPV was 97.6% (95% CI: 96.6%-98.3%) for men and 94.0% (95% CI: 92.9%-94.9%) for women, and the PPV increased with age at diagnosis. The PPV varied according to type of discharging departments, from 89.2% (95% CI: 83.4%-93.4%) in gynecology to 96.8% (95% CI: 94.9%-98.2%) in surgery, and was lower for outpatients compared with inpatients. We found a high PPV of the coding for anemia caused by bleeding in the DNRP. The registry is a valid source of data on anemia caused by bleeding for various purposes including research and monitoring health care.

  7. Next-Generation Sequencing of the HLA locus: Methods and impacts on HLA typing, population genetics and disease association studies.

    PubMed

    Carapito, Raphael; Radosavljevic, Mirjana; Bahram, Seiamak

    2016-11-01

    The human Major Histocompatibility Complex, known as the "Human Leukocyte Antigen (HLA)", could be defined as a "super locus" (historically called "supergene") governing the adaptive immune system in vertebrates. It also harbors genes involved in innate immunity. HLA is the most gene-dense, polymorphic and disease-associated region of the human genome. It is of critical medical relevance given its involvement in the fate of the transplanted organs/tissues and its association with more than 100 diseases. However, despite these important roles, comprehensive sequence analysis of the 4 megabase HLA locus has been limited due to technological challenges. Thanks to recent improvements in Next-Generation Sequencing (NGS) technologies however, one is now able to handle the peculiarities of the MHC notably the tight linkage disequilibrium between genes as well as their high degree of polymorphism (and hence heterozygosity). Increased read lengths, throughput, accuracy, as well as development of new bioinformatics tools now enable to efficiently generate complete and accurate full-length HLA haplotypes without phase ambiguities. The present report reviews current NGS approaches to capture, sequence and analyze HLA genes and loci. The impact of these new methodologies on various applications including HLA typing, population genetics and disease association studies are discussed. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  8. Anxiety, locus of control, and coping strategies among end-stage renal disease patients undergoing maintenance hemodialysis

    PubMed Central

    Kohli, S.; Batra, P.; Aggarwal, H. K.

    2011-01-01

    End-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD) have a lot of anxiety. Anxiety and coping are associated with the locus of control; the present investigation aimed to study the state and trait anxiety, locus of control, and active and passive coping among patients on MHD. Thirty MHD patients and 30 controls were administered State–Trait Anxiety Inventory, Rotter's Locus of Control Scale, and Coping Responses Inventory. There were significantly higher scores on state and trait anxiety, respectively (67.53 ± 10.89 vs. 59.40 ± 6.97, P < 0.01, and 62.97 ± 8.45 vs. 58.07 ± 7.06, P < 0.05), and locus of control (11.27 ± 3.55 vs. 9.04 ± 1.86, P < 0.01) in patients as compared to controls. On coping responses, patients and controls differed on positive reappraisal (54.33 ± 4.67 vs. 51.17 ± 3.12, P < 0.01), seeking guidance and support (58.07 ± 5.51 vs. 53.27 ± 4.22, P < 0.01), problem solving (51.03 ± 4.70 vs. 47.57 ± 4.73, P < 0.01), cognitive avoidance (60.27 ± 6.76 vs. 56.80 ± 4.08, P < 0.05), acceptance or resignation (61.67 ± 6.30 vs. 58.83 ± 4.23, P < 0.01), emotional discharge (68.07 ± 6.78 vs. 64.30 ± 4.50, P < 0.05), approach coping (205.57 ± 10.55 vs. 189.70 ± 11.37, P < 0.01), and avoidance coping (255.30 ± 16.45 vs. 241.10 ± 10.50, P < 0.01). A higher prevalence of anxiety trait could be the cause of anxiety in MHD patients besides the medical problems. The locus of control among patients though a mixed one was significantly more toward externalism. Thus, there is a need to identify this group well in advance and prepared not only medically but also psychologically for MHD. PMID:21886977

  9. A NOVEL ALZHEIMER DISEASE LOCUS LOCATED NEAR THE GENE ENCODING TAU PROTEIN

    PubMed Central

    Jun, Gyungah; Ibrahim-Verbaas, Carla A.; Vronskaya, Maria; Lambert, Jean-Charles; Chung, Jaeyoon; Naj, Adam C.; Kunkle, Brian W.; Wang, Li-San; Bis, Joshua C.; Bellenguez, Céline; Harold, Denise; Lunetta, Kathryn L.; Destefano, Anita L.; Grenier-Boley, Benjamin; Sims, Rebecca; Beecham, Gary W.; Smith, Albert V.; Chouraki, Vincent; Hamilton-Nelson, Kara L.; Ikram, M. Arfan; Fievet, Nathalie; Denning, Nicola; Martin, Eden R.; Schmidt, Helena; Kamatani, Yochiro; Dunstan, Melanie L; Valladares, Otto; Laza, Agustin Ruiz; Zelenika, Diana; Ramirez, Alfredo; Foroud, Tatiana M.; Choi, Seung-Hoan; Boland, Anne; Becker, Tim; Kukull, Walter A.; van der Lee, Sven J.; Pasquier, Florence; Cruchaga, Carlos; Beekly, Duane; Fitzpatrick, Annette L.; Hanon, Oliver; Gill, Michael; Barber, Robert; Gudnason, Vilmundur; Campion, Dominique; Love, Seth; Bennett, David A.; Amin, Najaf; Berr, Claudine; Tsolaki, Magda; Buxbaum, Joseph D.; Lopez, Oscar L.; Deramecourt, Vincent; Fox, Nick C; Cantwell, Laura B.; Tárraga, Lluis; Dufouil, Carole; Hardy, John; Crane, Paul K.; Eiriksdottir, Gudny; Hannequin, Didier; Clarke, Robert; Evans, Denis; Mosley, Thomas H.; Letenneur, Luc; Brayne, Carol; Maier, Wolfgang; De Jager, Philip; Emilsson, Valur; Dartigues, Jean-François; Hampel, Harald; Kamboh, M. Ilyas; de Bruijn, Renee F.A.G.; Tzourio, Christophe; Pastor, Pau; Larson, Eric B.; Rotter, Jerome I.; O’Donovan, Michael C; Montine, Thomas J.; Nalls, Michael A.; Mead, Simon; Reiman, Eric M.; Jonsson, Palmi V.; Holmes, Clive; St George-Hyslop, Peter H.; Boada, Mercè; Passmore, Peter; Wendland, Jens R.; Schmidt, Reinhold; Morgan, Kevin; Winslow, Ashley R.; Powell, John F; Carasquillo, Minerva; Younkin, Steven G.; Jakobsdóttir, Jóhanna; Kauwe, John SK; Wilhelmsen, Kirk C.; Rujescu, Dan; Nöthen, Markus M; Hofman, Albert; Jones, Lesley; Haines, Jonathan L.; Psaty, Bruce M.; Van Broeckhoven, Christine; Holmans, Peter; Launer, Lenore J.; Mayeux, Richard; Lathrop, Mark; Goate, Alison M.; Escott-Price, Valentina; Seshadri, Sudha; Pericak-Vance, Margaret A.; Amouyel, Philippe; Williams, Julie; van Duijn, Cornelia M.; Schellenberg, Gerard D.; Farrer, Lindsay A.

    2015-01-01

    APOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer’s Project (IGAP) Consortium in APOE ε4+ (10,352 cases and 9,207 controls) and APOE ε4− (7,184 cases and 26,968 controls) subgroups as well as in the total sample testing for interaction between a SNP and APOE ε4 status. Suggestive associations (P<1x10−4) in stage 1 were evaluated in an independent sample (stage 2) containing 4,203 subjects (APOE ε4+: 1,250 cases and 536 controls; APOE ε4-: 718 cases and 1,699 controls). Among APOE ε4− subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 datasets (best SNP, rs2732703, P=5·8x10−9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100 kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4− subjects (MS4A6A/MS4A4A/ MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6x10−7) is noteworthy because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3x10−8), frontal cortex (P≤1.3x10−9), and temporal cortex (P≤1.2x10−11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively

  10. A novel Alzheimer disease locus located near the gene encoding tau protein.

    PubMed

    Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M; Lambert, J-C; Chung, J; Naj, A C; Kunkle, B W; Wang, L-S; Bis, J C; Bellenguez, C; Harold, D; Lunetta, K L; Destefano, A L; Grenier-Boley, B; Sims, R; Beecham, G W; Smith, A V; Chouraki, V; Hamilton-Nelson, K L; Ikram, M A; Fievet, N; Denning, N; Martin, E R; Schmidt, H; Kamatani, Y; Dunstan, M L; Valladares, O; Laza, A R; Zelenika, D; Ramirez, A; Foroud, T M; Choi, S-H; Boland, A; Becker, T; Kukull, W A; van der Lee, S J; Pasquier, F; Cruchaga, C; Beekly, D; Fitzpatrick, A L; Hanon, O; Gill, M; Barber, R; Gudnason, V; Campion, D; Love, S; Bennett, D A; Amin, N; Berr, C; Tsolaki, Magda; Buxbaum, J D; Lopez, O L; Deramecourt, V; Fox, N C; Cantwell, L B; Tárraga, L; Dufouil, C; Hardy, J; Crane, P K; Eiriksdottir, G; Hannequin, D; Clarke, R; Evans, D; Mosley, T H; Letenneur, L; Brayne, C; Maier, W; De Jager, P; Emilsson, V; Dartigues, J-F; Hampel, H; Kamboh, M I; de Bruijn, R F A G; Tzourio, C; Pastor, P; Larson, E B; Rotter, J I; O'Donovan, M C; Montine, T J; Nalls, M A; Mead, S; Reiman, E M; Jonsson, P V; Holmes, C; St George-Hyslop, P H; Boada, M; Passmore, P; Wendland, J R; Schmidt, R; Morgan, K; Winslow, A R; Powell, J F; Carasquillo, M; Younkin, S G; Jakobsdóttir, J; Kauwe, J S K; Wilhelmsen, K C; Rujescu, D; Nöthen, M M; Hofman, A; Jones, L; Haines, J L; Psaty, B M; Van Broeckhoven, C; Holmans, P; Launer, L J; Mayeux, R; Lathrop, M; Goate, A M; Escott-Price, V; Seshadri, S; Pericak-Vance, M A; Amouyel, P; Williams, J; van Duijn, C M; Schellenberg, G D; Farrer, L A

    2016-01-01

    APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe

  11. [The assessment of the level of coping style and health locus of control in patients with coronary heart disease and hypertension].

    PubMed

    Opuchlik, Katarzyna; Wrzesińska, Magdalena; Kocur, Józef

    2009-01-01

    The assessment of the level of coping style and health locus of control in patients with coronary heart disease and hypertension. The sample studied consisted of 112 patients (81 M, 31 F) at the age of 35-65 years. Two groups participated in the study; first with coronary heart disease and hypertension and second with hypertension without other diseases. The Coping Inventory for Stressful Situation and Multidimensional Health Locus of Control Scale were used in the study. Two groups of patients used the most frequent task-oriented coping style. The significant differences were seen between groups in the external health locus of control (t = 2.113; p < 0.05); patients with coronary heart disease and hypertension revealed the strongest conviction that their health depended on other people. Patients with coronary heart disease and hypertension choose the task-oriented coping style. Patients with hypertension declare for internal health locus of control. Patients with coronary heart disease and hypertension declare for external locus of control.

  12. Identification of a chromosome 8p locus for early-onset coronary heart disease in a French Canadian population.

    PubMed

    Engert, James C; Lemire, Mathieu; Faith, Janet; Brisson, Diane; Fujiwara, T Mary; Roslin, Nicole M; Brewer, Carl G; Montpetit, Alexandre; Darmond-Zwaig, Corinne; Renaud, Yannick; Doré, Carole; Bailey, Swneke D; Verner, Andrei; Tremblay, Gérald; St-Pierre, Julie; Bétard, Christine; Platko, Jill; Rioux, John D; Morgan, Kenneth; Hudson, Thomas J; Gaudet, Daniel

    2008-01-01

    Susceptibility to coronary heart disease (CHD) has long been known to exhibit familial aggregation, with heritability estimated to be greater than 50%. The French Canadian population of the Saguenay-Lac Saint-Jean region of Quebec, Canada is descended from a founder population that settled this region 300-400 years ago and this may provide increased power to detect genes contributing to complex traits such as CHD. Probands with early-onset CHD, defined by angiographically determined coronary stenosis, and their relatives were recruited from this population (average sibship size of 6.4). Linkage analysis was performed following a genome-wide microsatellite marker scan on 42 families with 284 individuals. Nonparametric linkage (NPL) analysis provided suggestive evidence for a CHD susceptibility locus on chromosome 8 with an NPL score of 3.14 (P=0.001) at D8S1106. Linkage to this locus was verified by fine mapping in an enlarged sample of 50 families with 320 individuals. This analysis provided evidence of linkage at D8S552 (NPL score=3.53, P=0.0003), a marker that maps to the same location as D8S1106. Candidate genes in this region, including macrophage scavenger receptor 1, farnesyl-diphosphate farnesyltransferase 1, fibrinogen-like 1, and GATA-binding protein 4, were resequenced in all coding exons in both affected and unaffected individuals. Association studies with variants in these and five other genes did not identify a disease-associated mutation. In conclusion, a genome-wide scan and additional fine mapping provide evidence for a locus on chromosome 8 that contributes to CHD in a French Canadian population.

  13. The role of ferric carboxymaltose in the treatment of iron deficiency anemia in patients with gastrointestinal disease

    PubMed Central

    Koduru, Pramoda; Abraham, Bincy P.

    2016-01-01

    Iron deficiency anemia (IDA) is the most common form of nutritional anemia worldwide. Iron plays a pivotal role in vital functioning of almost every organ system. IDA affects both physical and psychological functioning of humans. Oral iron is considered as first-line therapy for the treatment of IDA due to low cost, good safety profile and ease of administration. However, the absorption of oral iron is affected by several factors and incidence of gastrointestinal side effects can lead to lack of adherence to therapy as well as poor efficacy. This has led to the emergence of intravenous iron therapy which is clearly superior to oral iron with higher increment of hemoglobin levels and rapid replenishment of iron stores. Ferric carboxymaltose (FCM) is a novel non-dextran intravenous iron form which has been approved for use in patients with iron deficiency who have had inadequate response to oral iron therapy, intolerance to oral iron, or nondialysis-dependent chronic kidney disease. The safety and efficacy of using FCM for the treatment of IDA has been demonstrated in several clinical trials. One dose can provide a large amount of iron and has a very short infusion time. It should be considered as first-line therapy in patients with active inflammation like inflammatory bowel disease when gastrointestinal absorption of oral iron may be compromised. It should also be given to patients who have inadequate response to oral iron therapy. It has been shown to be noninferior to other intravenous iron formulations with a good safety profile and produced fewer anaphylactic reactions. PMID:26770269

  14. Anemia of inflammation.

    PubMed

    Roy, Cindy N

    2010-01-01

    Inflammation arising from various etiologies, including infection, autoimmune disorders, chronic diseases, and aging, can promote anemia. The anemia of inflammation (AI) is most often normocytic and normochromic and is usually mild. Characteristic changes in systemic iron handling, erythrocyte production, and erythrocyte life span all contribute to AI. The preferred treatment is directed at the underlying disease. However, when the inflammatory insult is intractable, or the cause has not been diagnosed, there are limited options for treatment of AI. Because anemia is a comorbid condition that is associated with poor outcomes in various chronic disease states, understanding its pathogenesis and developing new tools for its treatment should remain a priority. Hepcidin antimicrobial peptide has taken center stage in recent years as a potent modulator of iron availability. As the technology for quantitative hepcidin analysis improves, hepcidin's role in various disease states is also being revealed. Recent insights concerning the regulatory pathways that modify hepcidin expression have identified novel targets for drug development. As the field advances with such therapeutics, the analysis of the impact of normalized hemoglobin on disease outcomes will confirm whether anemia is a reversible independent contributor to the morbidity and mortality associated with inflammatory diseases.

  15. Delta-He, Ret-He and a New Diagnostic Plot for Differential Diagnosis and Therapy Monitoring of Patients Suffering from Various Disease-Specific Types of Anemia.

    PubMed

    Weimann, Andreas; Cremer, Malte; Hernáiz-Driever, Pablo; Zimmermann, Mathias

    2016-01-01

    The present study was aimed to prove the usefulness of a new diagnostic plot (Hema-Plot), illustrating the relationship between the hemoglobin content of reticulocytes (Ret-He) as a marker of functional iron deficiency and the difference between the reticulocyte and erythrocyte hemoglobin content (Delta-He) as a marker of an impaired hemoglobinization of newly formed reticulocytes occurring during inflammatory processes, to differentiate between various disease-specific types of anemia. A complete blood and reticulocyte count was performed on routine EDTA blood samples from 345 patients with and without various disease-specific types of anemia using the Sysmex XN-9000 hematology analyzer: blood healthy newborns (n = 23), blood healthy adults (n = 31), patients suffering from anemia of chronic disease (ACD) due to diverse oncological, chronic inflammatory, or autoimmune diseases (total n = 138) with (n = 65) and without therapy (n = 73), patients with thalassemia and/or hemoglobinopathy (n = 18), patients with iron deficiency anemia (IDA) (n = 35), patients with a combination of ACD and IDA (n = 17), as well as patients suffering from sepsis (total n = 83) with (n = 32) and without therapy (n = 51). The results for Ret-He, Delta-He, and C-reactive protein (CRP) were statistically compared (Mann-Whitney U Test) between the particular patient groups and the diagnostic plots were drawn. Delta-Hemoglobin showed a statistically significant difference between blood healthy newborns and blood healthy adults (p ≤ 0.05), while Ret-He and C-reactive protein did not. In addition, of all three biomarkers only Delta-He showed a statistically significant difference (p ≤ 0.05) between the ACD/IDA and IDA cohort. Delta-He, Ret-He, and CRP showed a statistically significant difference between patient cohorts with and without therapy suffering from ACD, ACD/IDA, and sepsis before and after medical therapy (p ≤ 0.05). The Hema-Plot illustrated the dynamic character of Ret-He and

  16. Major hematologic diseases in the developing world- new aspects of diagnosis and management of thalassemia, malarial anemia, and acute leukemia.

    PubMed

    Greenberg, P L; Gordeuk, V; Issaragrisil, S; Siritanaratkul, N; Fucharoen, S; Ribeiro, R C

    2001-01-01

    The three presentations in this session encompass clinical, pathophysiological and therapeutic aspects of hematologic diseases which impact most heavily on developing world countries. Dr. Victor Gordeuk discusses new insights regarding the multi-faceted pathogenesis of anemia in the complicated malaria occurring in Africa. He describes recent investigations indicating the possible contribution of immune dysregulation to this serious complication and the implications of these findings for disease management. Dr. Surapol Issaragrisil and colleagues describe epidemiologic and clinical characteristics of the thalassemic syndromes. In addition to being considered a major health problem in Southeast Asia, the migration throughout the world of people from this region has caused the disease to have global impact. A unique thalassemia variant, Hb Ebeta-thalassemia, with distinctive clinical features, has particular relevance for this demographic issue. Special focus will be reported regarding recent prenatal molecular screening methods in Thailand which have proven useful for early disease detection and disease control strategies. Dr. Raul Ribeiro describes a clinical model for providing effective treatment for a complex malignancy (childhood acute lymphoblastic leukemia) in countries with limited resources. With the multidisciplinary approach in Central American of the joint venture between St. Jude Children's Research Hospital International Outreach Program and indigenous health care personnel, major therapeutic advances for this disease have been achieved. Given the major demographic population shifts occurring worldwide, these illnesses also have important clinical implications globally. These contributions demonstrate that lessons learned within countries of disease prevalence aid our understanding and management of a number of disorders prominently seen in developed countries. They will show how effective partnerships between hematologists in more and less developed

  17. Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics.

    PubMed

    Bogliolo, Massimo; Surrallés, Jordi

    2015-08-01

    Fanconi anemia (FA) is characterized by bone marrow failure, malformations, and chromosome fragility. We review the recent discovery of FA genes and efforts to develop genetic therapies for FA in the last five years. Because current data exclude FANCM as an FA gene, 15 genes remain bona fide FA genes and three (FANCO, FANCR and FANCS) cause an FA like syndrome. Monoallelic mutations in 6 FA associated genes (FANCD1, FANCJ, FANCM, FANCN, FANCO and FANCS) predispose to breast and ovarian cancer. The products of all these genes are involved in the repair of stalled DNA replication forks by unhooking DNA interstrand cross-links and promoting homologous recombination. The genetic characterization of patients with FA is essential for developing therapies, including hematopoietic stem cell transplantation from a savior sibling donor after embryo selection, gene therapy, or genome editing using genetic recombination or engineered nucleases. Newly acquired knowledge about FA promises to provide therapeutic strategies in the near future.

  18. Pseudomoyamoya in sickle cell anemia.

    PubMed

    Garza-Mercado, R

    1982-12-01

    Sickle cell (drepanocytic) anemia is a hereditary blood disease occurring very rarely in Mexico. A 13-year-old Mexican boy with sickle cell anemia eventually died of a cerebrovascular accident of the brain stem, as shown by computerized tomography (CT). A characteristic moyamoya-like angiographic pattern was demonstrated on bilateral carotid and left vertebral arteriograms. Moyamoya disease has no known etiology, but the characteristic angiographic features of moyamoya have been observed in conjunction with some other disease of known origin (including sickle cell anemia). It is therefore my belief that these latter cases should be referred to as pseudomoyamoya and not true moyamoya.

  19. Iron Deficiency Anemia in Pregnancy.

    PubMed

    Breymann, Christian

    2015-10-01

    Anemia is a common problem in obstetrics and perinatal care. Any hemoglobin below 10.5 g/dL can be regarded as true anemia regardless of gestational age. Reasons for anemia in pregnancy are mainly nutritional deficiencies, parasitic and bacterial diseases, and inborn red blood cell disorders such as thalassemias. The main cause of anemia in obstetrics is iron deficiency, which has a worldwide prevalence between estimated 20%-80% and consists of a primarily female population. Stages of iron deficiency are depletion of iron stores, iron-deficient erythropoiesis without anemia, and iron deficiency anemia, the most pronounced form of iron deficiency. Pregnancy anemia can be aggravated by various conditions such as uterine or placental bleedings, gastrointestinal bleedings, and peripartum blood loss. In addition to the general consequences of anemia, there are specific risks during pregnancy for the mother and the fetus such as intrauterine growth retardation, prematurity, feto-placental miss ratio, and higher risk for peripartum blood transfusion. Besides the importance of prophylaxis of iron deficiency, the main therapy options for the treatment of pregnancy anemia are oral iron and intravenous iron preparations.

  20. Clinico-aetiologic profile of macrocytic anemias with special reference to megaloblastic anemia.

    PubMed

    Unnikrishnan, Vineetha; Dutta, Tarun Kumar; Badhe, Bhawana A; Bobby, Zachariah; Panigrahi, Ashish K

    2008-12-01

    This study was conducted to study the clinical and laboratory parameters in patients with macrocytic anemia and to determine the etiology of macrocytic anemia with special reference to megaloblastic anemia. This study was a cross-sectional descriptive study carried over a period of 18 months on 60 adult patients (age ≥13 years) of macrocytic anemia. Macrocytic anemia was identified when peripheral blood examination showed anemia with a mean red blood corpuscular volume of >95 fl. The most common cause of macrocytic anemia was megaloblastic anemia (38.4%). The major causes of nonmegaloblastic macrocytic anemia were primary bone marrow disorders (35%), liver diseases (15%) and hemolytic anemia (8.3%). There was a significant male preponderance in the study (65%). The megaloblastic anemias observed were due to either vitamin B(12) deficiency (78.3%) or combined B(12) and folate deficiency (21.7%). A significant proportion of non-vegetarians (73.9%) had megaloblastic anemia. Patients with an MCV of >110fl were more likely to have megaloblastic anemia (p value 0.0007). Three patients (mean age 55 years) with a megaloblastic marrow did not respond to vitamin replacement and were found to have myelodysplastic syndrome. Megaloblastic anemia due to Vitamin B(12) or folate deficiency remains the most important cause of macrocytic anemia. In settings with limited laboratory facilities, a therapeutic trial of vitamins B(12) or folic acid is useful in determining the specific vitamin deficiency.

  1. Pernicious anemia

    MedlinePlus

    ... anemia include: Weakened stomach lining (atrophic gastritis) An autoimmune condition in which the body's immune system attacks the actual intrinsic factor protein or the cells in the lining of ...

  2. Hemolytic Anemia

    MedlinePlus

    ... Hemoglobin is an iron-rich protein that carries oxygen from the lungs to the rest of the body. Anemia has three main causes: blood loss, lack of red blood cell production, or high rates of red blood cell destruction. ...

  3. Association analysis revealed one susceptibility locus for vitiligo with immune-related diseases in the Chinese Han population.

    PubMed

    Li, Shu; Yao, Weiyi; Pan, Qian; Tang, Xianfa; Zhao, Suli; Wang, Wenjun; Zhu, Zhengwei; Gao, Jinping; Sheng, Yujun; Zhou, Fusheng; Zheng, Xiaodong; Zuo, Xianbo; Sun, Liangdan; Zhang, Anping

    2015-07-01

    Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset.

  4. Transfusion burden in non-dialysis chronic kidney disease patients with persistent anemia treated in routine clinical practice: a retrospective observational study

    PubMed Central

    2012-01-01

    Background Transfusion patterns are not well characterized in non-dialysis (ND) chronic kidney disease (CKD) patients. This study describes the proportion of patients transfused, units of blood transfused and trigger-hemoglobin (Hb) levels for transfusions in severe anemic, ND-CKD patients in routine practice. Methods A retrospective cohort study of electronic medical record data from the Henry Ford Health System identified 374 adult, ND-CKD patients with severe anemia (Hb < 10 g/dL and subsequent use of erythropoiesis-stimulating agents [ESA] therapy, blood transfusions, or a second Hb < 10 g/dL) between January 2004 and June 2008. Exclusions included those with prior diagnoses of cancer, renal or liver transplant, end-stage renal disease, acute bleeding, trauma, sickle cell disease, or aplastic anemia. A gap of ≥ 1 days between units of blood transfused was counted as a separate transfusion. Results At least 1 transfusion (mean of 2 units; range, 1-4) was administered to 20% (75/374) of ND-CKD patients with mean (± SD) follow-up of 459 (± 427) days. The mean (± SD) Hb level closest and prior to a transfusion was 8.8 (± 1.5) g/dL. Patients who were hospitalized in the 6 months prior to their first anemia diagnosis were 6.3 times more likely to receive a blood transfusion than patients who were not hospitalized (p < 0.0001). Patients with peripheral vascular disease (PVD) were twice as likely to have a transfusion as patients without PVD (p = 0.04). Conclusions Transfusions were prevalent and the trigger hemoglobin concentration was approximately 9 g/dL among ND-CKD patients with anemia. To reduce the transfusion burden, clinicians should consider other anemia treatments including ESA therapy. PMID:22273400

  5. A cluster of four receptor-like genes resides in the Vf locus that confers resistance to apple scab disease.

    PubMed Central

    Xu, Mingliang; Korban, Schuyler S

    2002-01-01

    The Vf locus, derived from the crabapple species Malus floribunda 821, confers resistance to five races of the fungal pathogen Venturia inaequalis, the causal agent of apple scab disease. In our previous research, the Vf locus was restricted to a BAC contig of approximately 290 kb covered by five overlapping BAC clones. Here, we report on cloning of the resistance gene(s) present in the Vf BAC contig using a highly reliable and straightforward approach. This approach relies on hybridization of labeled cDNAs to amplified inserts of subclones derived from BAC inserts, followed by recovery of full-size transcripts by rapid amplification of cDNA ends (RACE). A cluster of four resistance paralogs (Vfa1, Vfa2, Vfa3, and Vfa4) was identified in the Vf locus. Vfa1, Vfa2 and Vfa4 had no introns and are predicted to encode proteins characterized with extracellular leucine-rich repeats (LRRs) and transmembrane (TM) domains. However, Vfa3 contains an insertion of 780 bp at the end of the LRR motif, resulting in multiple truncated transcripts. Comparison of Vfa1, Vfa2, and Vfa4 paralogs revealed a high degree of overall homology in their deduced amino acid sequences, while divergences were mainly restricted within LRR domains, including variable LRR units, numerous amino acid substitutions, and several residue deletions/duplications. Differential expression profiles among the four paralogs were observed during leaf development. Vfa1, Vfa2, and Vfa3 were active in immature leaves, but slightly expressed in mature leaves, while Vfa4 was active in immature leaves and was highly expressed in mature leaves. PMID:12524365

  6. A cluster of four receptor-like genes resides in the Vf locus that confers resistance to apple scab disease.

    PubMed

    Xu, Mingliang; Korban, Schuyler S

    2002-12-01

    The Vf locus, derived from the crabapple species Malus floribunda 821, confers resistance to five races of the fungal pathogen Venturia inaequalis, the causal agent of apple scab disease. In our previous research, the Vf locus was restricted to a BAC contig of approximately 290 kb covered by five overlapping BAC clones. Here, we report on cloning of the resistance gene(s) present in the Vf BAC contig using a highly reliable and straightforward approach. This approach relies on hybridization of labeled cDNAs to amplified inserts of subclones derived from BAC inserts, followed by recovery of full-size transcripts by rapid amplification of cDNA ends (RACE). A cluster of four resistance paralogs (Vfa1, Vfa2, Vfa3, and Vfa4) was identified in the Vf locus. Vfa1, Vfa2 and Vfa4 had no introns and are predicted to encode proteins characterized with extracellular leucine-rich repeats (LRRs) and transmembrane (TM) domains. However, Vfa3 contains an insertion of 780 bp at the end of the LRR motif, resulting in multiple truncated transcripts. Comparison of Vfa1, Vfa2, and Vfa4 paralogs revealed a high degree of overall homology in their deduced amino acid sequences, while divergences were mainly restricted within LRR domains, including variable LRR units, numerous amino acid substitutions, and several residue deletions/duplications. Differential expression profiles among the four paralogs were observed during leaf development. Vfa1, Vfa2, and Vfa3 were active in immature leaves, but slightly expressed in mature leaves, while Vfa4 was active in immature leaves and was highly expressed in mature leaves.

  7. eQTL analysis links inflammatory bowel disease associated 1q21 locus to ECM1 gene.

    PubMed

    Repnik, Katja; Potočnik, Uroš

    2016-08-01

    Genome-wide association studies (GWAS) have been highly successful in inflammatory bowel disease (IBD) with 163 confirmed associations so far. We used expression quantitative trait loci (eQTL) mapping to analyze IBD associated regions for which causative gene from the region is still unknown. First, we performed an extensive literature search and in silico analysis of published GWAS in IBD and eQTL studies and extracted 402 IBD associated SNPs assigned to 208 candidate loci, and 9562 eQTL correlations. When crossing GWA and eQTL data we found that for 50 % of loci there is no eQTL gene, while for 31.2 % we can determine one gene, for 11.1 % two genes and for the remaining 7.7 % three or more genes. Based on that we selected loci with one, two, and three or more eQTL genes and analyzed them in peripheral blood lymphocytes and intestine tissue samples of 606 Slovene patients with IBD and in 449 controls. Association analysis of selected SNPs showed statistical significance for three (rs2631372 and rs1050152 on 5q locus and rs13294 on 1q locus) out of six selected SNPs with at least one phenotype. Furthermore, with eQTL analysis of selected chromosomal regions, we confirmed a link between SNP and gene for four (SLC22A5 on 5q, ECM1 on 1q, ORMDL3 on 17q, and PUS10 on 2p locus) out of five selected regions. For 1q21 loci, we confirmed gene ECM1 as the most plausible gene from this region to be involved in pathogenesis of IBD and thereby contributed new eQTL correlation from this genomic region.

  8. Nutritional anemias.

    PubMed

    Oski, F A

    1979-10-01

    The role of the metals, iron and copper, and the vitamins E, folic acid, and B12 in the genesis of nutritional anemias in infancy have been reviewed. All are preventable. The precise requirements for each of these trace elements and vitamins in the small premature infant remain to be defined. The nonhematologic consequences of these nutritional deficiencies require further study. Anemia may prove to be the least important manifestation of the deficiency states.

  9. Hemolytic disease of the fetus and newborn with late-onset anemia due to anti-M: a case report and review of the Japanese literature.

    PubMed

    Yasuda, Hiroyasu; Ohto, Hitoshi; Nollet, Kenneth E; Kawabata, Kinuyo; Saito, Shunnichi; Yagi, Yoshihito; Negishi, Yutaka; Ishida, Atsushi

    2014-01-01

    Hemolytic disease of the fetus and newborn (HDFN) attributed to M/N-incompatibility varies from asymptomatic to lethally hydropic. Case reports are rare, and the clinical significance of anti-M is not completely understood. A challenging case of HDFN due to anti-M prompted an investigation of the Japanese literature, in order to characterize the clinical spectrum of M/N-incompatibility pregnancies in Japan and report results to English-language readers. Japanese reports of HDFN attributed to M/N incompatibility were compiled. Abstracted data include maternal antibody titers at delivery, fetal direct antiglobulin test, hemoglobin, total bilirubin, reticulocyte count at birth, and therapeutic interventions. We investigated characteristics of HDFN due to M/N-incompatible pregnancies in Japan after encountering a case of severe HDFN along with late-onset anemia in an infant born to a woman carrying IgG anti-M with a titer of 1. In total, thirty-three babies with HDFN due to anti-M and one due to anti-N have been reported in Japan since 1975. The median maternal antibody titer was 64 at delivery and was 16 or less in 10 of 34 women (29%). Five of 34 babies (15%) were stillborn or died as neonates. Twenty-one of 29 survivors (72%) had severe hemolytic anemia and/or hydrops fetalis. The reticulocyte count of neonates with anemia stayed below the reference interval. Sixteen (55%) developed late-onset anemia and 14 (48%) were transfused with M-negative RBCs. Significant positive correlation (P < .05) between the hemoglobin value and the reticulocyte count within 4 days of birth was obtained in 16 babies with anti-M HDFN. In the Japanese population, 21 of 34 cases of M/N-incompatible HDFN (72%) have manifested as severe hemolytic anemia and/or hydrops fetalis. Low reticulocyte count in neonates with late-onset anemia is consistent with suppressed erythropoiesis due to anti-M.

  10. Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia

    PubMed Central

    Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M.; Liu, Baoying; Knickelbein, Jared; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G.; Kaplan, Mariana J.; Nussenblatt, Robert B.; Barrett, A. John; O’Shea, John; Young, Neal S.

    2015-01-01

    Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4+ and CD8+ T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8+ TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8+ TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8+ TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-γ and IL-2 production was significantly increased in various CD8+ and CD4+ T cell subsets in AA patients, including CD8+ and CD4+ TSCMs. CD8+ TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4+ and CD8+ TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8+ TSCM subset is a novel biomarker and a potential therapeutic target for AA. PMID:26764034

  11. Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia.

    PubMed

    Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M; Liu, Baoying; Knickelbein, Jared; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G; Kaplan, Mariana J; Nussenblatt, Robert B; Barrett, A John; O'Shea, John; Young, Neal S

    2016-02-15

    Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4(+) and CD8(+) T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8(+) TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8(+) TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8(+) TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-γ and IL-2 production was significantly increased in various CD8(+) and CD4(+) T cell subsets in AA patients, including CD8(+) and CD4(+) TSCMs. CD8(+) TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4(+) and CD8(+) TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8(+) TSCM subset is a novel biomarker and a potential therapeutic target for AA.

  12. Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.

    PubMed

    Sponseller, Brett A; Sparks, Wendy O; Wannemuehler, Yvonne; Li, Yuxing; Antons, Amanda K; Oaks, J Lindsay; Carpenter, Susan

    2007-06-20

    The principal neutralizing domain (PND) of equine infectious anemia virus (EIAV) is located in the V3 region of SU. Genetic variation in the PND is considered to play an important role in immune escape and EIAV persistence; however, few studies have characterized genetic variation in SU during the inapparent stage of disease. To better understand the mechanisms of virus persistence, we undertook a longitudinal study of SU variation in a pony experimentally inoculated with the virulent EIAV(Wyo). Viral RNA isolated from the inoculum and from sequential sera samples was amplified by RT-PCR, cloned, and individual clones were sequenced. Of the 147 SU clones obtained, we identified 71 distinct V3 variants that partitioned into five major non-overlapping groups, designated PND-1 to PND-5, which segregated with specific stages of clinical disease. Genotypes representative of each group were inserted into an infectious molecular clone, and chimeric viruses were tested for susceptibility to neutralization by autologous sera from successive times post-infection. Overall, there was a trend for increasing resistance to neutralizing antibody during disease progression. The PND genotype associated with recrudescence late in infection was resistant to both type-specific and broadly neutralizing antibody, and displayed a reduced replication phenotype in vitro. These findings indicate that neutralizing antibody exerts selective pressure throughout infection and suggest that viral strategies of immune evasion and persistence change in the face of an evolving and maturing host immune response.

  13. Mapping of the chromosome 1p36 region surrounding the Charcot-Marie-Tooth disease type 2A locus

    SciTech Connect

    Denton, P.; Gere, S.; Wolpert, C.

    1994-09-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Although CMT2 is clinically indistinguishable from CMT1, the two forms can be differentiated by pathological and neurophysiological methods. We have established one locus, CMT2A on chromosome 1p36, and have established genetic heterogeneity. This locus maps to the region of the deletions associated with neuroblastoma. We have now identified an additional 11 CMT2 families. Three families are linked to chromosome 1p36 while six families are excluded from this region. Another six families are currently under analysis and collection. To date the CMT2A families represent one third of those CMT2 families examined. We have established a microdissection library of the 1p36 region which is currently being characterized for microsatellite repeats and STSs using standard hybridization techniques and a modified degenerate primer method. In addition, new markers (D1S253, D1S450, D1S489, D1S503, GATA27E04, and GATA4H04) placed in this region are being mapped using critical recombinants in the CEPH reference pedigrees. Fluorescent in situ hybridization (FISH) has been used to confirm mapping. A YAC contig is being assembled from the CEPH megabase library using STSs to isolate key YACs which are extended by vectorette end clone and Alu-PCR. These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrates further heterogeneity in the CMT phenotype.

  14. What Is Aplastic Anemia?

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Aplastic Anemia? Aplastic anemia (a-PLAS-tik uh-NEE-me-uh) is ... heart, heart failure , infections, and bleeding. Severe aplastic anemia can even cause death. Overview Aplastic anemia is ...

  15. The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval.

    PubMed

    Zimprich, Alexander; Müller-Myhsok, Bertram; Farrer, Matthew; Leitner, Petra; Sharma, Manu; Hulihan, Mary; Lockhart, Paul; Strongosky, Audrey; Kachergus, Jennifer; Calne, Donald B; Stoessl, Jon; Uitti, Ryan J; Pfeiffer, Ronald F; Trenkwalder, Claudia; Homann, Nikolaus; Ott, Erwin; Wenzel, Karoline; Asmus, Friedrich; Hardy, John; Wszolek, Zbigniew; Gasser, Thomas

    2004-01-01

    Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission for linkage in this region. Criteria for inclusion were at least three affected individuals in more than one generation. A total of 29 markers were used to saturate the candidate region. One hundred sixty-seven family members were tested (84 affected and 83 unaffected). Under the assumption of heterogeneity and through use of an affecteds-only model, a maximum multipoint LOD score of 2.01 was achieved in the total sample, with an estimated proportion of families with linkage of 0.32. This LOD score is significant for linkage in a replication study and corresponds to a P value of.0047. Two families (family A [German Canadian] and family D [from western Nebraska]) reached significant linkage on their own, with a combined maximum multipoint LOD score of 3.33, calculated with an affecteds-only model (family A: LOD score 1.67, P=.0028; family D: LOD score 1.67, P=.0028). When a penetrance-dependent model was calculated, the combined multipoint LOD score achieved was 3.92 (family A: LOD score 1.68, P=.0027; family D: LOD score 2.24, P=.0007). On the basis of the multipoint analysis for the combined families A and D, the 1-LOD support interval suggests that the most likely disease location is between a CA repeat polymorphism on genomic clone AC025253 (44.5 Mb) and marker D12S1701 (47.7 Mb). Our data provide evidence that the PARK8 locus is responsible for the disease in a subset of families of white ancestry with autosomal dominant parkinsonism, suggesting that it could be a more common locus.

  16. Sickle cell anemia: a potential nutritional approach for a molecular disease.

    PubMed

    Ohnishi, S T; Ohnishi, T; Ogunmola, G B

    2000-05-01

    A certain population of red blood cells in patients with sickle cell anemia has an elevated density and possesses an abnormal membrane. These "dense cells" have a tendency to adhere to neutrophils, platelets, and vascular endothelial cells, and, thus, they could trigger vasoocclusion and the subsequent painful crisis from which these patients suffer. We developed a laboratory method of preparing such dense cells and found that nutritional antioxidant supplements, hydroxyl radical scavengers, and iron-binding agents could inhibit the formation of dense cells in vitro. The concentrations at which effective nutritional supplements could inhibit dense cell formation by 50% were 4.0 mg/mL for aged garlic extract, 0.38 mg/mL for black tea extract, 0.13 mg/mL for green tea extract, 0.07 mg/mL for Pycnogenol, 930 microM for alpha-lipoic acid, 270 microM for vitamin E, 45 microM for coenzyme Q(10), and 32 microM for beta-carotene. Both an ex vivo study and a pilot clinical trial demonstrated that a cocktail consisting of daily doses of 6 g of aged garlic extract, 4-6 g of vitamin C, and 800 to 1200 IU of vitamin E may indeed be beneficial to the patients.

  17. Relapsing catastrophic antiphospholipid syndrome potential role of microangiopathic hemolytic anemia in disease relapses.

    PubMed

    Espinosa, Gerard; Rodríguez-Pintó, Ignasi; Gomez-Puerta, José A; Pons-Estel, Guillermo; Cervera, Ricard

    2013-02-01

    To analyze the clinical and laboratory characteristics of patients with catastrophic antiphospholipid syndrome (APS) who suffer relapses. We analyzed the Web site--based international registry of patients with catastrophic APS ("CAPS Registry") http://infmed.fcrb.es/es/web/caps and selected those cases that relapsed. Relapses were reported in 9 of 282 (3.2%) patients with catastrophic APS. A total of 35 episodes of catastrophic APS were found: 6 patients presented 2 relapses, 2 patients suffered 3 relapses, and 1 patient developed 17 relapses. However, the last patient was not included in the statistical analysis because his clinical and immunologic characteristics were not fully described. Therefore, a total of 18 episodes were analyzed. In 9 (50%) episodes, a precipitating factor was identified. The most frequent precipitating factor, found in 5 (28%) episodes, was infection. Brain, kidney, heart, and lung were the most common organs involved. Laboratory features of microangiopathic hemolytic anemia (MHA) were present in 13 of 18 (72%) episodes (definitive in 9, corresponding to 4 patients, and probable in 4, corresponding to 2 patients). Three relapses did not present with features of MHA and in the remaining 2 these data were not reported. The mortality rate was 38%. Although relapses are rare in patients with catastrophic APS, these results support the hypothesis that an association between MHA and relapsing of catastrophic APS could be present. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Transmission of equine infectious anemia virus from horses without clinical signs of disease.

    PubMed

    Issel, C J; Adams, W V; Meek, L; Ochoa, R

    1982-02-01

    Twenty seven adult horses positive to the agar gel immunodiffusion (AGID) test for equine infectious anemia (EIA), but with no history of clinical EIA, were used in transfusion studies to determine whether infectious EIA virus was present in 1 to 5 ml of their blood. Of 27 recipients, 21 (78%) became AGID test-positive at an average of 24 days after inoculation. Two horses that were initially negative when screened were retested and found to carry infectious virus in 5-300 ml of whole blood; the other 4 horses were not retested. Horse flies (Tabanus fuscicostatus Hine) were unable to transmit EIA virus from 10 AGID test-positive donors with no history of clinical EIA, but virus was transmitted from a pony with artificially induced acute EIA and from a horse that had recovered from a clinical attack of EIA 9 months earlier. Histopathologic changes indicative of EIA were noted in all test-positive recipients. The most consistent lesion was paracortical lymphoid hyperplasia in the splenic lymph node.

  19. [Microcytic and hypochromic anemias].

    PubMed

    Chrobák, L

    2001-03-01

    In the majority of cases, microcytosis is the result of impaired hemoglobin synthesis. Disorders of iron metabolism and protoporphyrin and heme synthesis, as well as impaired globin synthesis, lead to defective hemoglobin production and to the generation of microcytosis and microcytic anemia. Iron deficiency anemie, anemia of chronic diseases, thalassemias, congenital sideroblastic anemias and homozygous HbE disease are the main representatives of microcytosis and microcytic anemias. Serum iron, total iron binding capacity, transferrin saturation, serum ferritin, serum transferrin receptor, transferrin receptor-ferritin index, and zinc-protoporhyrin concentration in erythrocytes are tests used for assessment of iron deficiency. The convention laboratory test for diagnosing iron deficiency is the measurement of serum ferritin. The most precise method for evaluating body iron stores is the examination for iron on aspirated bone marrow or marrow biopsy. Increased content of Hb A2 over 3.5% is diagnostic for beta-thalassemia. Presence of ringed sideroblasts is characteristic of sideroblastic anemias. Hemoglobin electrophoresis is required for the diagnosis of hemoglobinopathy E. The optimal therapeutic regimen in iron deficiency anemia used in this country is to administer 100 mg of elemental iron twice daily separately from meals. Ferrous sulphate (Ferronat Retard tbl. or Sorbifer Dulures tbl.) which are slow-releasing iron formulations are preferred because of their low cost, high bioavailability and low side-effects. Parenteral iron therapy is justified only in patients who cannot absorb iron, who have blood losses that exceed the maximal absorptive capacity of their intestinal tract or who are totally intolerant of oral iron. However, parenteral iron therapy may be associated with serious and even fatal side-effects.

  20. Treatment of anemia with erythropoietin-stimulating agents in kidney transplant recipients and chronic kidney disease-another drawback of immunosuppression?

    PubMed

    Malyszko, J; Glowinska, I; Mysliwiec, M

    2012-12-01

    Anemia is more prevalent in allograft recipients compared with glomerular filtration rate (GFR) matched patients with chronic kidney diseases. There is a paucity of data concerning the correction of anemia in the posttransplant period with erythropoietin-stimulating agents (ESA). The aim of this study was to compare the iron status, kidney function, inflammatory state, use of drugs affecting erythropoiesis (immunosuppressants ACEi/ARB) and correction of anemia using ESA in a chronic kidney disease (CKD) population versus kidney transplant recipients. We included 67 patients treated with ESA including 17 after kidney transplantation. CKD Patients with native kidneys were significantly older than allograft recipients (mean age 69 versus 51 years; P < .001, and despite similar serum creatinine and iron parameters showed an estimated lower GFR (19 mL/min versus 23 mL/min; P < .05). Median time of ESA therapy was similar among patients with native kidney CKD versus kidney recipients, but they achieved a significantly higher hemoglobin (11.04 versus 10.36 g/dL; P < .05). There was no difference between patients administered or not a mammalian target of rapamycin antagonist. None of the patients with native kidney CKD received immunosuppressive therapy, but they were prescribed ACEi more often than kidney recipients. The higher degree of anemia in kidney allograft recipient is the most probably attributed to the use of immunosuppressive drugs, despite their better kidney function and comparable iron status. This study suggested that higher doses of ESA should be employed to anemia in kidney transplant recipients. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Study of large inbred Friedreich ataxia families reveals a recombination between D9S15 and the disease locus

    SciTech Connect

    Belal, S.; Ben Hamida, C.; Hentati, F.; Ben Hamida, M. ); Panayides, K.; Ioannou, P.; MIddleton, L.T. ); Sirugo, G.; Koenig, S.; Mandel, J.L ); Beckmann, J. )

    1992-12-01

    Friedreich ataxia is a neurodegenerative disorder with autosomal recessive inheritance. Precise linkage mapping of the Friedreich ataxia locus (FRDA) in 9q13-q21 should lead to the isolation of the defective gene by positional cloning. The two closest DNA markers, D9S5 and D9S15, show very tight linkage to FRDA, making difficult the ordering of the three loci. The authors present a linkage study of three large Friedreich ataxia families of Tunisian origin, with several multiallelic markers around D9S5 and D9S15. Haplotype data were used to investigate genetic homogeneity of the disease in these geographically related families. A meiotic recombination was found in a nonaffected individual, which excludes a 150-kb segment, including D9S15, as a possible location for the Freidreich ataxia gene and which should orient the search in the D9S5 region. 16 refs., 1 fig., 1 tab.

  2. Parenteral iron use in the management of anemia in end-stage renal disease patients.

    PubMed

    Bailie, G R; Johnson, C A; Mason, N A

    2000-01-01

    Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

  3. Iron Indices in Patients with Functional Anemia in Chronic Kidney Disease

    PubMed Central

    Reddy, G. Chinnapu; Rao, Pragna

    2014-01-01

    Background Despite high ferritin level, HDCKD patients may have functional iron deficiency even after intravenous iron (iv) therapy. The aim of this study was to test the hypothesis that lowered serum transferrin level may contribute to functional anemia and erythropoietin hypo responsiveness by the failure to transport accumulated tissue iron to the relevant target tissue. Materials and methods The study subjects were divided into four groups. Group-A: HDCKD Patients receiving iv iron (n=290). Group-B: Patients not initiated on to hemodialysis (NDCKD), and received oral iron (n=38). Group-C: HDCKD patients with erythropoietin hypo responsiveness (n=9). Group-D: Healthy controls (n=36). The group-A, patients were sub-divided into five groups (A-1 to A-5) based on their serum ferritin levels. Results Serum ferritin and tissue iron levels in group-A and C patients were significantly greater than the group-D(p<0.0001) and group-B patients(p<0.001). Transferrin level of group-A and C showed lowered values and consequently a higher %TSAT when compared to group-D. The percent of patients with iron overload was 2.6%, 31%, and 44% in group-B, group-A and group-C respectively. Serum transferrin level significantly correlated with TIBC in group-A and B patients (p<0.0001;p<0.05 respectively). Transferrin level significantly correlated with TIBC in all subgroups of HDCKD(p<0.05) with the exception in subgroup-A2 and with hemoglobin in subgroups A3 (p<0.05) and A5(p<0.01) respectively. Conclusions The lowered transferrin level prevents the proper transport of the iron to the hematopoietic sites, which may be a reason for the low hemoglobin synthesis and also for the development of erythropoietin hypo responsiveness in some of the dialysis patients. PMID:27683448

  4. Epidemiology of anemia in heart failure.

    PubMed

    Tang, W H Wilson; Yeo, P S Daniel

    2010-07-01

    Anemia is being increasingly recognized as an important comorbidity in patients with heart failure. Despite wide variations in defining anemia, approximately one-fifth to one-third of patients with heart failure may experience anemia at a given time. The prevalence may increase to more than half of patients in the setting of severe heart failure, and it may differ with different settings. Meanwhile, up to a fifth of patients may experience new-onset anemia, even though most cases may resolve over time. Different factors contribute to the development of anemia, including increasing age, renal insufficiency, hemodilution, chronic inflammation, and increasing heart failure disease severity.

  5. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L.

    PubMed

    Patel, Sheetal; Monemian, Seyed; Khalid, Ayesha; Dosik, Harvey

    2011-01-01

    Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  6. Renal disease in adult Nigerians with sickle cell anemia: a report of prevalence, clinical features and risk factors.

    PubMed

    Bolarinwa, R A; Akinlade, K S; Kuti, M A O; Olawale, O O; Akinola, N O

    2012-01-01

    Renal abnormalities in adult Nigerians with sickle cell anemia (SCA) have not been extensively studied. To determine the prevalence, pattern and the associated risk factors of renal disease, 72 subjects with SCA from two centers in the southwestern Nigeria were investigated. Socio-demographic data, body mass index and clinical findings were documented. The urine analysis, serum bio-chemistry, hemogram and renal factors attributable to SCA were determined. Presence of albuminuria of at least 1+ or microalbuminuria in those negative with dipstick; and the estimated glomerular filtration rate (eGFR) using the Cockcroft-Gault formula categorized subjects to various stages of chronic kidney disease (CKD). Subjects with and without albuminuria were compared to determine the relative risk associated with renal disease. Four (5.6%) subjects had macro-albuminuria, while 32 (44.4%) had micro-albuminuria and 30 (41.7%) had hemoglobinuria. In the subjects with albuminuria, age, hematocrit, systolic blood pressure, serum creatinine, urea and creatinine clearance were numerically higher while the eGFR was numerically lower. There was no significant difference in the clinical parameters studied in the two groups of subjects. The diastolic blood pressure was significantly higher in the albuminuric group. Based on eGFR, 22 (30.6%) subjects had hyperfiltration (GFR > 140 mL/min/1.73 m2), of whom 36.4% had albuminuria, 18 (25.0%) had stage 1 CKD, 30 (41.7%) had stage 2 CKD and two (2.7%) subjects had stage 3 CKD with albuminuria. None had stage 4 and 5 CKD. We conclude that renal abnormalities, importantly albuminuria, is common in adult Nigerians with SCA and the pattern and incidence are similar to those reported from other parts of the world. Regular blood pressure monitoring, early diagnosis and active intervention are advocated to delay progression to end-stage kidney disease in view of poor outcomes of renal replacement therapy in SCA patients with nephropathy.

  7. A 2-month-old boy with hemolytic anemia and reticulocytopenia following intravenous immunoglobulin therapy for Kawasaki disease: a case report and literature review

    PubMed Central

    Kim, Na Yeon; Kim, Joon Hwan; Park, Jin Suk; Kim, Soo Hyun; Cho, Yeon Kyung; Cha, Dong Hyun; Kim, Ki Eun; Kang, Myung Suh; Lim, Kyung Ah

    2016-01-01

    Herein, we report a rare case of hemolytic anemia with reticulocytopenia following intravenous immunoglobulin therapy in a young infant treated for Kawasaki disease. A 2-month-old boy presented with fever lasting 3 days, conjunctival injection, strawberry tongue, erythematous edema of the hands, and macular rash, symptoms and signs suggestive of incomplete Kawasaki disease. His fever resolved 8 days after treatment with aspirin and high dose infusion of intravenous immunoglobulin. The hemoglobin and hematocrit decreased from 9.7 g/dL and 27.1% to 7.4 g/dL and 21.3%, respectively. The patient had normocytic hypochromic anemia with anisocytosis, poikilocytosis, immature neutrophils, and nucleated red blood cells. The direct antiglobulin test result was positive, and the reticulocyte count was 1.39%. The patient had an uneventful recovery. However, reticulocytopenia persisted 1 month after discharge. PMID:28018448

  8. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

    PubMed

    Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

    2011-11-01

    Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD.

  9. Targeted sequencing of the Paget's disease associated 14q32 locus identifies several missense coding variants in RIN3 that predispose to Paget's disease of bone

    PubMed Central

    Vallet, Mahéva; Soares, Dinesh C.; Wani, Sachin; Sophocleous, Antonia; Warner, Jon; Salter, Donald M.; Ralston, Stuart H.; Albagha, Omar M.E.

    2015-01-01

    Paget's disease of bone (PDB) is a common disorder with a strong genetic component characterized by increased but disorganized bone remodelling. Previous genome-wide association studies identified a locus on chromosome 14q32 tagged by rs10498635 which was significantly associated with susceptibility to PDB in several European populations. Here we conducted fine-mapping and targeted sequencing of the candidate locus to identify possible functional variants. Imputation in 741 PDB patients and 2699 controls confirmed that the association was confined to a 60 kb region in the RIN3 gene and conditional analysis adjusting for rs10498635 identified no new independent signals. Sequencing of the RIN3 gene identified a common missense variant (p.R279C) that was strongly associated with the disease (OR = 0.64; P = 1.4 × 10−9), and was in strong linkage disequilibrium with rs10498635. A further 13 rare missense variants were identified, seven of which were novel and detected only in PDB cases. When combined, these rare variants were over-represented in cases compared with controls (OR = 3.72; P = 8.9 × 10−10). Most rare variants were located in a region that encodes a proline-rich, intrinsically disordered domain of the protein and many were predicted to be pathogenic. RIN3 was expressed in bone tissue and its expression level was ∼10-fold higher in osteoclasts compared with osteoblasts. We conclude that susceptibility to PDB at the 14q32 locus is mediated by a combination of common and rare coding variants in RIN3 and suggest that RIN3 may contribute to PDB susceptibility by affecting osteoclast function. PMID:25701875

  10. Administrative database concerns: accuracy of International Classification of Diseases, Ninth Revision coding is poor for preoperative anemia in patients undergoing spinal fusion.

    PubMed

    Golinvaux, Nicholas S; Bohl, Daniel D; Basques, Bryce A; Grauer, Jonathan N

    2014-11-15

    Cross-sectional study. To objectively evaluate the ability of International Classification of Diseases, Ninth Revision (ICD-9) codes, which are used as the foundation for administratively coded national databases, to identify preoperative anemia in patients undergoing spinal fusion. National database research in spine surgery continues to rise. However, the validity of studies based on administratively coded data, such as the Nationwide Inpatient Sample, are dependent on the accuracy of ICD-9 coding. Such coding has previously been found to have poor sensitivity to conditions such as obesity and infection. A cross-sectional study was performed at an academic medical center. Hospital-reported anemia ICD-9 codes (those used for administratively coded databases) were directly compared with the chart-documented preoperative hematocrits (true laboratory values). A patient was deemed to have preoperative anemia if the preoperative hematocrit was less than the lower end of the normal range (36.0% for females and 41.0% for males). The study included 260 patients. Of these, 37 patients (14.2%) were anemic; however, only 10 patients (3.8%) received an "anemia" ICD-9 code. Of the 10 patients coded as anemic, 7 were anemic by definition, whereas 3 were not, and thus were miscoded. This equates to an ICD-9 code sensitivity of 0.19, with a specificity of 0.99, and positive and negative predictive values of 0.70 and 0.88, respectively. This study uses preoperative anemia to demonstrate the potential inaccuracies of ICD-9 coding. These results have implications for publications using databases that are compiled from ICD-9 coding data. Furthermore, the findings of the current investigation raise concerns regarding the accuracy of additional comorbidities. Although administrative databases are powerful resources that provide large sample sizes, it is crucial that we further consider the quality of the data source relative to its intended purpose.

  11. Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn's Disease Patients and Unaffected First-Degree Relatives.

    PubMed

    Gloux, Karine; Anba-Mondoloni, Jamila

    2016-01-01

    Crohn's disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn's disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn's disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn's disease.

  12. Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn’s Disease Patients and Unaffected First-Degree Relatives

    PubMed Central

    Gloux, Karine; Anba-Mondoloni, Jamila

    2016-01-01

    Crohn’s disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn’s disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn’s disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn’s disease. PMID:26824357

  13. Intravenous iron dextran as a component of anemia management in chronic kidney disease: a report of safety and efficacy.

    PubMed

    Yessayan, Lenar; Sandhu, Ankur; Besarab, Anatole; Yessayan, Alexy; Frinak, Stan; Zasuwa, Gerard; Yee, Jerry

    2013-01-01

    Objective. We aimed to demonstrate safety and efficacy of intravenous (IV) low molecular weight iron dextran (LMWID) during treatment of anemic stage 3 and 4 chronic kidney disease (CKD) patients. Methods. Efficacy data was obtained by retrospective chart review of 150 consecutively enrolled patients. Patients were assigned per protocol to oral or IV iron, with IV iron given to those with lower iron stores and/or hemoglobin. Iron and darbepoetin were administered to achieve and maintain hemoglobin at 10-12 g/dL. Efficacy endpoints were mean hemoglobin and change in iron indices approximately 30 and 60 days after enrollment. Safety data was obtained by retrospective review of reported adverse drug events (ADEs) following 1699 infusions of LMWID (0.5-1.0 g). Results. Mean hemoglobin, iron saturation, and ferritin increased significantly from baseline to 60 days in patients assigned to LMWID (hemoglobin: 11.3 versus 9.4 g/dL; iron saturation: 24% versus 12.9%; ferritin: 294.7 versus 134.7 ng/mL; all P  values < 0.0001). Iron stores and hemoglobin were maintained in the group assigned to oral iron. Of 1699 iron dextran infusions, three ADEs occurred. Conclusions. Treatment of anemia in CKD stages 3 and 4 with LMWID and darbepoetin is efficacious. The serious ADE rate was 0.06% per infusion.

  14. A clinical case of chicken infectious anemia disease and virus DNA detection in naturally infected broilers in Greece.

    PubMed

    Bougiouklis, P A; Sofia, M; Brellou, G; Georgopoulou, I; Billinis, C; Vlemmas, I

    2007-06-01

    In this study, chicken infectious anemia virus (CIAV) DNA was detected from 12-day-old broilers. Clinical history showed that the clinical features were diarrhea, blue wing disease, depression, and death. Necropsy findings were pale liver, severe atrophy of bursa of Fabricius and thymus, and discoloration of the bone marrow as well as hemorrhages subcutaneously and a few in skeletal muscles. The majority of the necropsied broilers had developed gangrenous dermatitis. Histopathology showed hypoplasia of bone marrow and depletion of lymphocytes in spleen, bursa, and subcapsular thymic cortex. Karyorrhexis of lymphocytes was scattered in the thymic cortex and most pronounced in the bursal follicles. Eosinophilic intranuclear inclusion bodies were mainly located in lymphocytes of thymus, with a few in hemopoietic cells of bone marrow. CIAV DNA was detected by polymerase chain reaction from bursa, thymus, and bone marrow. A virus strain was detected and genetically characterized in 639 base pairs of VP1 gene. Phylogenetic analysis revealed that the Greek isolate was clustered together with isolates from Alabama, China, Slovenia, and Bangladesh.

  15. Ferumoxytol: a new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease.

    PubMed

    Schwenk, Michael H

    2010-01-01

    Ferumoxytol is an intravenous iron preparation for treatment of the anemia of chronic kidney disease (CKD). It is a carbohydrate-coated, superparamagnetic iron oxide nanoparticle. Because little free iron is present in the preparation, doses of 510 mg have been administered safely in as little as 17 seconds. Two prospective, randomized studies compared two doses of ferumoxytol 510 mg given in 5 +/- 3 days with 3 weeks of oral iron 200 mg/day (as ferrous fumarate) in anemic patients with CKD. One study enrolled 304 patients with stages 1-5 CKD (predialysis), and the other study enrolled 230 patients with stage 5D CKD (undergoing hemodialysis). In both studies, a greater increase in hemoglobin level from baseline to end of study (day 35) was noted in patients who received ferumoxytol compared with those who received oral iron (mean +/- SD 0.82 +/- 1.24 vs 0.16 +/- 1.02 g/dl in patients with stages 1-5 CKD and 1.02 +/- 1.13 vs 0.46 +/- 1.06 g/dl in patients with stage 5D CKD, p<0.001). A greater proportion of both predialysis and hemodialysis patients who received ferumoxytol had hemoglobin level increases from baseline of 1 g/dl or more compared with those who received oral iron (p<0.001). In a prospective, double-blind, crossover study of more than 700 patients with CKD stages 1-5D that compared the safety of ferumoxytol with normal saline injection, the rates of treatment-related adverse events were 5.2% and 4.5%, respectively. Serious treatment-related adverse events were seen in one patient in each treatment group. The most common adverse events with ferumoxytol occurred at the injection site (bruising, pain, swelling, erythema). Dizziness, nausea, pruritus, headache, and fatigue occurred in less than 2% of patients receiving ferumoxytol, with a similar frequency noted after administration of normal saline. In short-term studies, intravenous ferumoxytol was safely and rapidly administered, and was more effective than oral iron therapy in increasing hemoglobin

  16. Bed bugs reproductive life cycle in the clothes of a patient suffering from Alzheimer's disease results in iron deficiency anemia.

    PubMed

    Sabou, Marcela; Imperiale, Delphine Gallo; Andrès, Emmanuel; Abou-Bacar, Ahmed; Foeglé, Jacinthe; Lavigne, Thierry; Kaltenbach, Georges; Candolfi, Ermanno

    2013-01-01

    We report the case of an 82-year-old patient, hospitalized for malaise. Her clothes were infested by numerous insects and the entomological analysis identified them as being Cimex lectularius (bed bugs). The history of the patient highlighted severe cognitive impairment. The biological assessment initially showed a profound microcytic, aregenerative, iron deficiency anemia. A vitamin B12 deficiency due to pernicious anemia (positive intrinsic factor antibodies) was also highlighted, but this was not enough to explain the anemia without macrocytosis. Laboratory tests, endoscopy and a CT scan eliminated a tumor etiology responsible for occult bleeding. The patient had a mild itchy rash which was linked to the massive colonization by the bed bugs. The C. lectularius bite is most often considered benign because it is not a vector of infectious agents. Far from trivial, a massive human colonization by bed bugs may cause such a hematic depletion that severe microcytic anemia may result.

  17. Gestational anemia.

    PubMed

    Wahed, F; Latif, S A; Nessa, A; Bhuiyan, M R; Hossain, M B; Akther, A; Mahmud, M M

    2010-07-01

    Gestational anemia is a common public health problem in our country. Most anemia during pregnancy results from an increased need for iron as her body is making more blood. Often dietary supplementation does not provide enough iron to meet the extra needs. Also the growing baby takes all the iron it needs from mother, regardless of how much iron is stored in mother's blood. Gestational Anemia contributed significantly to maternal morbidity and mortality, IUGR, preterm delivery and perinatal morbidity and mortality. A high proportion of women in both industrialized and developing countries become anemic during pregnancy. The most important cause of gestational anemia due to iron deficiency, because high iron requirements during pregnancy are not easily fulfilled by dietary intake. Adequate iron stores can help a pregnant women replace lost red blood cells. So, iron supplementation is strongly recommended for all pregnant women in developing countries. Oral iron intake is the treatment of choice and almost all pregnant women can be treated effectively with oral iron preparation during their pregnancy period.

  18. Coexistence of megaloblastic anemia and iron deficiency anemia in a young woman with chronic lymphocytic thyroiditis.

    PubMed

    Chen, Shih-Hsiang; Hung, Chia-Sui; Yang, Chao-Ping; Lo, Fu-Sung; Hsu, Hsun-Hui

    2006-10-01

    Pernicious anemia is a megaloblastic anemia caused by vitamin B12 deficiency, and is the end-stage of autoimmune gastritis that typically affects persons older than 60 years. It is the most common cause of vitamin B12 deficiency. Pernicious anemia can also be diagnosed concurrently with other autoimmune diseases. We report the occurrence of megaloblastic anemia in a 22-year-old woman with chronic autoimmune thyroiditis for 10.5 years. Recently, she presented with microcytic anemia, and iron deficiency anemia was diagnosed initially. After administration of ferrous sulfate, macrocytic anemia was revealed and vitamin B12 deficiency was detected. Pernicious anemia was highly suspected because of the endoscopic finding of atrophic gastritis, and high titer of antigastric parietal cell antibody, as well as elevated serum gastrin level. After intramuscular injections of hydroxycobalamine 100 microg daily for 10 days, and monthly later, her blood counts returned to normal.

  19. [Hemolytic anemias and vitamin B12 deficieny].

    PubMed

    Dietzfelbinger, Hermann; Hubmann, Max

    2015-08-01

    Hemolytic anemias consist of corpuscular, immun-hemolytic and toxic hemolytic anemias. Within the group of corpuscular hemolytic anemias, except for the paroxysmal nocturnal hemoglobinuria (PNH), all symptoms are caused by underlying heredetiary disorders within the red blood cell membran (hereditary spherocytosis), deficiencies of red cell enzymes (G6PDH- and pyrovatkinase deficiency) or disorders in the hemoglobin molecule (thalassaemia and sickle cell disease). Immune-hemolytic anemias are acquired hemolytic anemias and hemolysis is caused by auto- or allo-antibodies which are directed against red blood cell antigens. They are classified as warm, cold, mixed type or drug-induced hemolytic anemia. Therapy consists of glucocorticoids and other immunsuppressive drugs. Pernicious anemia is the most important vitamin B12 deficiency disorder. Diagnosis relies on cobalamin deficiency and antibodies to intrinsic factor. The management should focus on a possibly life-long replacement treatment with cobalamin.

  20. Sexuality and sickle cell anemia

    PubMed Central

    Côbo, Viviane de Almeida; Chapadeiro, Cibele Alves; Ribeiro, João Batista; Moraes-Souza, Helio; Martins, Paulo Roberto Juliano

    2013-01-01

    Background Sickle cell disease, the most common hereditary blood disease in the world, is the result of an atypical hemoglobin called S (Hb S) which, when homozygous (Hb SS) is the cause of sickle cell anemia. Changes of puberty, correlated with a delayed growth spurt, begin late in both male and female sickle cell anemia individuals with repercussions on sexuality and reproduction. The objectives of this exploratory and descriptive study were to characterize the development of sexuality in adults with sickle cell anemia by investigating the patient's perception of their sex life, as well as the information they had and needed on this subject. Methods Twenty male and female sickle cell anemia patients treated at the Hemocentro Regional de Uberaba (UFTM) with ages between 19 and 47 years old were enrolled. A socioeconomic questionnaire and a semi-structured interview on sexuality, reproduction and genetic counseling were applied. Results This study shows that the sickle cell anemia patients lacked information on sexuality especially about the risks of pregnancy and the possible inheritance of the disease by their children. Moreover, the sexual life of the patients was impaired due to pain as well as discrimination and negative feelings experienced in close relationships. Conclusion The health care of sickle cell anemia patients should take into account not only the clinical aspects of the disease, but also psychosocial aspects by providing counseling on sexuality, reproduction and genetics, in order to give this population the possibility of a better quality of life. PMID:23741184

  1. A radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia disease locus

    SciTech Connect

    Richard, C.W. III; Cox, D.R.; Kapp, L.; Murnane, J. ); Cornelis, F.; Julier, C.; Lathrop, M.; James, M.R. )

    1993-07-01

    The authors describe a high-resolution radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia (AT) disease gene loci. The order and intermarker distances of 32 chromosome 11q22-q23 markers were determined by a multipoint maximum likelihood method analysis of the cosegregation of markers in 100 radiation hybrids. The radiation hybrid map of polymorphic loci was consistent with genetic linkage maps of common markers. Several genes, including [alpha]B-crystallin, adrenal ferrodoxin, CBL2, collagenase, dopamine receptor type 2, neural cell adhesion molecule, progesterone receptor, and stromelysins 1 and 2, were placed in relation to previously ordered, genetically mapped polymorphic loci. Five new markers ([alpha]B-crystallin, adrenal ferrodoxin, CJ52.114, CJ52.3, and D11S535) were ordered within the current published flanking markers for the AT group A and group C disease loci. A candidate AT group D gene (ATDC) identified by Kapp et al. was mapped telomeric to THY1, outside the flanking markers identified by multipoint linkage analysis for the major AT locus. 29 refs., 1 fig., 2 tabs.

  2. The Prevalence and Management of Anemia in Chronic Kidney Disease Patients: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

    PubMed Central

    2017-01-01

    Anemia is a common and significant complication of chronic kidney disease (CKD). However, its prevalence and current management status has not been studied thoroughly in Korea. We examined the prevalence of anemia, its association with clinical and laboratory factors, and utilization of iron agents and erythropoiesis stimulating agents using the baseline data from the large-scale CKD cohort in Korea. We defined anemia when hemoglobin level was lower than 13.0 g/dL in males and 12.0 g/dL in females, or received by erythropoiesis stimulating agents. Overall prevalence of anemia was 45.0% among 2,198 non-dialysis CKD patients from stage 1 to 5. Diabetic nephropathy (DN) as a cause, CKD stages, body mass index (BMI), smoking, leukocyte count, serum albumin, iron markers, calcium, and phosphorus concentration were identified as independent risk factors for anemia. Considering the current coverage of Korean National Health Insurance System, only 7.9% among applicable patients were managed by intravenous iron agents, and 42.7% were managed by erythropoiesis stimulating agents. PMID:28049235

  3. Abnormal expression of inflammatory genes in placentas of women with sickle cell anemia and sickle hemoglobin C disease.

    PubMed

    Baptista, Letícia C; Costa, Maria Laura; Ferreira, Regiane; Albuquerque, Dulcinéia M; Lanaro, Carolina; Fertrin, Kleber Y; Surita, Fernanda G; Parpinelli, Mary A; Costa, Fernando F; Melo, Mônica Barbosa de

    2016-10-01

    Sickle cell disease (SCD) is a complex disease that is characterized by the polymerization of deoxyhemoglobin S, altered red blood cell membrane biology, endothelial activation, hemolysis, a procoagulant state, acute and chronic inflammation, and vaso-occlusion. Among the physiological changes that occur during pregnancy, oxygen is consumed by fetal growth, and pregnant women with SCD are more frequently exposed to low oxygen levels. This might lead to red blood cells sickling, and, consequently, to vaso-occlusion. The mechanisms by which SCD affects placental physiology are largely unknown, and chronic inflammation might be involved in this process. This study aimed to evaluate the gene expression profile of inflammatory response mediators in the placentas of pregnant women with sickle cell cell anemia (HbSS) and hemoglobinopathy SC (HbSC). Our results show differences in a number of these genes. For the HbSS group, when compared to the control group, the following genes showed differential expression: IL1RAP (2.76-fold), BCL6 (4.49-fold), CXCL10 (-2.12-fold), CXCR1 (-3.66-fold), and C3 (-2.0-fold). On the other hand, the HbSC group presented differential expressions of the following genes, when compared to the control group: IL1RAP (4.33-fold), CXCL1 (3.05-fold), BCL6 (4.13-fold), CXCL10 (-3.32-fold), C3 (-2.0-fold), and TLR3 (2.38-fold). Taken together, these data strongly suggest a differential expression of several inflammatory genes in both SCD (HbSS and HbSC), indicating that the placenta might become an environment with hypoxia, and increased inflammation, which could lead to improper placental development.

  4. A new machine learning approach for predicting the response to anemia treatment in a large cohort of End Stage Renal Disease patients undergoing dialysis.

    PubMed

    Barbieri, Carlo; Mari, Flavio; Stopper, Andrea; Gatti, Emanuele; Escandell-Montero, Pablo; Martínez-Martínez, José M; Martín-Guerrero, José D

    2015-06-01

    Chronic Kidney Disease (CKD) anemia is one of the main common comorbidities in patients undergoing End Stage Renal Disease (ESRD). Iron supplement and especially Erythropoiesis Stimulating Agents (ESA) have become the treatment of choice for that anemia. However, it is very complicated to find an adequate treatment for every patient in each particular situation since dosage guidelines are based on average behaviors, and thus, they do not take into account the particular response to those drugs by different patients, although that response may vary enormously from one patient to another and even for the same patient in different stages of the anemia. This work proposes an advance with respect to previous works that have faced this problem using different methodologies (Machine Learning (ML), among others), since the diversity of the CKD population has been explicitly taken into account in order to produce a general and reliable model for the prediction of ESA/Iron therapy response. Furthermore, the ML model makes use of both human physiology and drug pharmacology to produce a model that outperforms previous approaches, yielding Mean Absolute Errors (MAE) of the Hemoglobin (Hb) prediction around or lower than 0.6 g/dl in the three countries analyzed in the study, namely, Spain, Italy and Portugal. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Hereditary sideroblastic anemia: pathophysiology and gene mutations.

    PubMed

    Harigae, Hideo; Furuyama, Kazumichi

    2010-10-01

    Sideroblastic anemia is characterized by anemia with the emergence of ring sideroblasts in the bone marrow. Ring sideroblasts are erythroblasts characterized by iron accumulation in perinuclear mitochondria due to impaired iron utilization. There are two forms of sideroblastic anemia, i.e., inherited and acquired sideroblastic anemia. Inherited sideroblastic anemia is a rare and heterogeneous disease caused by mutations of genes involved in heme biosynthesis, iron-sulfur (Fe-S) cluster biogenesis, or Fe-S cluster transport, and mitochondrial metabolism. The most common inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutations of the erythroid-specific δ-aminolevulinate synthase gene (ALAS2), which is the first enzyme of heme biosynthesis in erythroid cells. Sideroblastic anemia due to SLC25A38 gene mutations, which is a mitochondrial transporter, is the next most common inherited sideroblastic anemia. Other forms of inherited sideroblastic anemia are very rare, and accompanied by impaired function of organs other than hematopoietic tissue, such as the nervous system, muscle, or exocrine glands due to impaired mitochondrial metabolism. Moreover, there are still significant numbers of cases with genetically undefined inherited sideroblastic anemia. Molecular analysis of these cases will contribute not only to the development of effective treatment, but also to the understanding of mitochondrial iron metabolism.

  6. Coping Styles Mediate the Relationship Between Self-esteem, Health Locus of Control, and Health-Promoting Behavior in Chinese Patients With Coronary Heart Disease.

    PubMed

    Zou, Huijing; Tian, Qian; Chen, Yuxia; Cheng, Cheng; Fan, Xiuzhen

    Health-promoting behavior plays an important role in reducing the burden of coronary heart disease. Self-esteem and health locus of control may contribute to health-promoting behavior, and coping styles may mediate these associations. The aims of our study were to examine whether self-esteem and health locus of control are associated with health-promoting behavior and examine the possible mediating effect of coping styles in patients with coronary heart disease. Health-promoting behavior, self-esteem, health locus of control, and coping styles were assessed in 272 hospitalized patients (60 ± 12 years, 61% male) with coronary heart disease. Hierarchical regression analysis was conducted to analyze the relationships between health-promoting behavior and other variables. Mediation effect was examined according to the methods of Baron and Kenny. The mean score for health-promoting behavior was 2.57 ± 0.51; 38.2% of patients (n = 104) scored lower than 2.5. Self-esteem (β = .139, P < .05), confrontation coping style (β = .491, P < .001), disease duration (≥6 months, β = .147, P < .05), and monthly income (≥1000 RMB [approximately US$154], β = .111, P < .05) were positively associated with health-promoting behavior, accounting for 47.5% of its variance (F = 19.828). Confrontation partly mediated the association between self-esteem and health-promoting behavior and completely mediated the relationship between internal health locus of control and health-promoting behavior. Confrontation plays a mediating role in the association among self-esteem, internal health locus of control, and health-promoting behavior. Strategies should be undertaken to encourage the use of confrontation coping style, which will facilitate health-promoting behavior.

  7. Determinants of serum high molecular weight (HMW) adiponectin levels in patients with coronary artery disease: associations with cardio-renal-anemia syndrome.

    PubMed

    Hara, Kenji; Uchida, Toshihiko; Takebayashi, Kohzo; Sakai, Yoshihiko; Inoue, Teruo; Inukai, Toshiko; Takayanagi, Kan; Aso, Yoshimasa

    2011-01-01

    A low serum adiponectin level is associated with a high incidence of coronary artery disease (CAD) in the healthy population. Paradoxically, serum adiponectin is elevated in patients with severe CAD or chronic heart failure. We investigated the determinants of serum high molecular weight (HMW) adiponectin in patients with CAD. We studied 228 consecutive patients with CAD confirmed by angiography. Anemia was defined as a hemoglobin of <13.0 g/dL in men and<12.0 g/dL in women. A high plasma B-type natriuretic-peptide (BNP) was defined as >100 pg/mL. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min for more than 3 months. The patients with CAD were divided into eight groups according to the presence or absence of anemia, high BNP, and/or CKD. In all 228 patients with CAD, serum HMW adiponectin correlated positively with age, high-density-lipoprotein cholesterol (HDL-C), and BNP, while this parameter showed negative correlations with body mass index, insulin resistance, triglycerides, eGFR, and hemoglobin. Multivariate analysis showed that HDL-C, BNP, gender, and age were independently associated with the HMW adiponectin. Serum HMW adiponectin was lower in CAD patients with than without metabolic syndrome. Serum HMW adiponectin and the HMW/total adiponectin ratio were highest in CAD patients who had anemia, high BNP, and CKD among the groups. In patients with CAD, metabolic syndrome is associated with a lower serum HMW adiponectin, while the presence of anemia, high BNP, and CKD is associated with elevation of the serum HMW adiponectin.

  8. Some epistatic two-locus models of disease. II. The confounding of linkage and association

    PubMed Central

    Hodge, Susan E.; Spence, M. Anne

    1981-01-01

    This paper continues to examine the model discussed in the preceding paper. Specifically, it will be shown how a linkage analysis performed in the presence of a disease-marker association can give rise to erroneous and misleading results. PMID:6941696

  9. A putative quantitative trait locus on chromosome 20 associated with bovine pathogenic disease incidence

    USDA-ARS?s Scientific Manuscript database

    The objective was to detect QTL associated with the incidence of multiple pathogenic diseases in offspring from half-sib bovine families. Four F1 sires were used to produce offspring: Brahman x Hereford (BH; n = 547), Piedmontese x Angus (PA; n = 209), Brahman x Angus (BA; n = 176), and Belgian Blu...

  10. Prevalence of iron deficiency anemia in chronic diarrhoea and celiac disease - a western UP experience.

    PubMed

    Sherwani, Rana K; Alam, Seema; Akhtar, Kafil; Abid, Bushra; Rahman, Khaliqur; Mehdi, Riaz

    2008-03-01

    To study the prevalence of iron deficiency anaemia in chronic diarrhoea and celiac disease. Cases included 45 children between 1-12 years with chronic diarrhoea, who underwent investigations like haemogram with GBP, RBC indices, serum iron and TIBC. After a course of antibiotic therapy for 6 weeks with iron and folic acid with no improvement noted within 2 weeks, they were subjected to duodenal biopsy. If biopsy showed features of celiac disease, then anti-endomysial antibody test was performed to substantiate the diagnosis. 30 cases (66.7%) were males and 15 (33.3%) females. 8 cases (17.8%) had watery diarrhoea, 20 (44.4%) semiformed and 17 (37.8%) had watery and semiformed diarrhoea. Bloody diarrhoea was present in 5 (11.1%) and abdominal distension in 21 cases (46.7%). Pallor seen in all the cases. The mean age of the cases was 55 ± 1.5 months and mean duration of diarrhoea was 18 ± 1.4 months. Mean haemoglobin observed was 8.1 ± 1.6 gm%. MCV, MCH and MCHC were 79.1 ± 8.6 fl, 26.9 ± 3 pg and 29.6 ± 2.3 g/dl respectively. Mean serum iron was 32.1 ± 1.2 g/ dl and TIBC was 432 ± 3.2 g/ dl. On peripheral smear, 28 cases (82.4%) showed microcytic hypochromic anaemia. 26 cases showed evidence of celiac disease on duodenal biopsy. Anti endomysial antibody (AEA) test was positive in 15 of the 19 celiac cases on which performed. Mean duration of diarrhoea (23.5 months) was significantly more in celiacs as compared to non-celiacs (11.6 months). Better awareness of the clinical profile and early detection of celiac disease would help detection and management of iron deficiency anaemia associated with celiac disease.

  11. Inborn anemias in mice: (Annual report, 1983-1984)

    SciTech Connect

    Bernstein, S.E.

    1984-09-01

    The hypotranserrinemic-hemochromatosis mutation in mice discovered in our laboratory is an almost exact duplicate of human atransferrinemia. Just as in man, the condition is inherited as a recessive lethal. The disease appears to stem from a congenital deficiency in transferrin. The new mutation arose spontaneously in BALB/c mice and results in death before 12 days of age. It is characterized by stunted growth, low numbers of erythrocytes, hypochromia, and in the absence of jaundice. Treatments with Imferon or other iron preparations were uniformly unsuccessful, but the use of normal mouse serum proved successful as a therapeutic measure. We find that we are able to keep these afflicted mice alive for more than a year with small amounts of normal serum, and transferrin bands are missing on cellulose acetate electrophoresis of serum proteins from affected individuals receiving no treatment. Genetic tests indicated that the new mutation was not an allele of any of the other known iron deficiency anemias in the mouse: sex linked anemia (sla), microcytic anemia (mk), or flexed anemia (f) or any of the members of the hemolytic disease group (sph, sph/sup ha/, nb, or ja). Biochemical and genetic analyses carried out during the past year indicate that the new mutation, tentatively designated hpx is not likely to be a mutation at the transferrin (Trf) locus on Chromosome 9. We observed no unusual serum proteins on cellulose acetate electrophoresis, such as might be expected if the Trf gene had mutated. Moreover, radial immunodiffusion examination and Ouchterlony analysis did not show the presence of smaller molecules (or fragments) with transferrin antigenic specificities. Instead they showed a total loss in serum transferrin. 14 refs., 5 tabs.

  12. Congenital sideroblastic anemia treated as thalassemia major.

    PubMed

    Chowdhury, R K; Miah, M Z; Morshed, M

    2010-10-01

    Sideroblastic anemia is a rare cause of microcytic hypochromic anemia. In Bangladesh, most common causes of microcytic anemia are iron deficiency anemia, anemia of chronic diseases and thalassemia. Serum ferritin is usually done to differentiate them. If serum ferritin is low, the diagnosis of iron deficiency is entertained. When serum ferritin is raised but erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are normal - anemia of chronic disease is excluded. The next investigation is Hb-electrophoresis. Normal Hb-electroporesis excludes thalassemia. Then bone marrow examination with iron stain is done for the diagnosis of sideroblastic anemia. Here we report a case of a 14 year old girl presenting with intermittent leg pain and anemia. Her blood flim showed microcytic hypochromic anemia with raised serum ferritin and normal Hb-electroporesis. Initially she was labeled as a case of unusual type of thalassemia and treated with blood transfusion. Finally bone marrow examination with iron stain was done and she was diagnosed as a case of congenital sideroblastic anemia. We reviewed the literature and discussed the management as well.

  13. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.

    PubMed

    Grupe, Andrew; Li, Yonghong; Rowland, Charles; Nowotny, Petra; Hinrichs, Anthony L; Smemo, Scott; Kauwe, John S K; Maxwell, Taylor J; Cherny, Sara; Doil, Lisa; Tacey, Kristina; van Luchene, Ryan; Myers, Amanda; Wavrant-De Vrièze, Fabienne; Kaleem, Mona; Hollingworth, Paul; Jehu, Luke; Foy, Catherine; Archer, Nicola; Hamilton, Gillian; Holmans, Peter; Morris, Chris M; Catanese, Joseph; Sninsky, John; White, Thomas J; Powell, John; Hardy, John; O'Donovan, Michael; Lovestone, Simon; Jones, Lesley; Morris, John C; Thal, Leon; Owen, Michael; Williams, Julie; Goate, Alison

    2006-01-01

    Strong evidence of linkage to late-onset Alzheimer disease (LOAD) has been observed on chromosome 10, which implicates a wide region and at least one disease-susceptibility locus. Although significant associations with several biological candidate genes on chromosome 10 have been reported, these findings have not been consistently replicated, and they remain controversial. We performed a chromosome 10-specific association study with 1,412 gene-based single-nucleotide polymorphisms (SNPs), to identify susceptibility genes for developing LOAD. The scan included SNPs in 677 of 1,270 known or predicted genes; each gene contained one or more markers, about half (48%) of which represented putative functional mutations. In general, the initial testing was performed in a white case-control sample from the St. Louis area, with 419 LOAD cases and 377 age-matched controls. Markers that showed significant association in the exploratory analysis were followed up in several other white case-control sample sets to confirm the initial association. Of the 1,397 markers tested in the exploratory sample, 69 reached significance (P < .05). Five of these markers replicated at P < .05 in the validation sample sets. One marker, rs498055, located in a gene homologous to RPS3A (LOC439999), was significantly associated with Alzheimer disease in four of six case-control series, with an allelic P value of .0001 for a meta-analysis of all six samples. One of the case-control samples with significant association to rs498055 was derived from the linkage sample (P = .0165). These results indicate that variants in the RPS3A homologue are associated with LOAD and implicate this gene, adjacent genes, or other functional variants (e.g., noncoding RNAs) in the pathogenesis of this disorder.

  14. Response of Iron Deficiency Anemia to Intravenous Iron Sucrose in Pediatric Inflammatory Bowel Disease

    PubMed Central

    2016-01-01

    OBJECTIVES: The objective of this retrospective study was to evaluate the safety and efficacy of intravenous iron sucrose (IS) in iron deficient children with inflammatory bowel disease (IBD) in remission. METHODS: Electronic medical records at a university based pediatric children's hospital were searched for patients in age range 0 to 18 years with diagnosis of IBD and treatment with IS over a 1-year period. Response to IS treatment was assessed by posttreatment changes in ferritin, hemoglobin (Hb), and mean corpuscular volume (MCV). Patients with recorded symptoms of active disease were excluded from analysis of treatment response. RESULTS: Twelve patients were identified by the search criteria, 10 with Crohn's disease (CD), 2 with ulcerative colitis (UC). Data represent 8 patients in remission, 7 with CD and 1 with UC, who received a total of 34 IS infusions. Iron sucrose was administered in cycles of 2 infusions, 2.5 to 3.5 mg/kg/dose (maximum 200 mg), 1 week apart. Mean ferritin increased from 21.4 ± 9.2 to 52.9 ± 10.1 ng/mL (p = 0.0005), Hb from 10.9 ± 0.4 to 11.3 ± 0.3 g/dL (p = 0.02), and MCV from 76.9 ± 2 to 79.4 ± 2 fl (p = 0.006). Iron sucrose treatment normalized ferritin in 6 of 7, Hb in 2 of 8, and MCV in 2 of 5 patients with low pretreatment levels. No adverse effects were recorded. CONCLUSIONS: Two IS infusions of 2.5 to 3.5 mg/kg/dose (maximum 200 mg), given 1 week apart normalized ferritin levels in most pediatric IBD patients in remission without adverse effects. Further studies are needed to determine optimal dosing schedules. PMID:27199624

  15. Response to intravenous iron in patients with iron deficiency anemia (IDA) and restless leg syndrome (Willis-Ekbom disease).

    PubMed

    Mehmood, Tahir; Auerbach, Michael; Earley, Christopher J; Allen, Richard P

    2014-12-01

    Iron deficiency anemia (IDA) engenders restless legs syndrome (RLS, aka Willis-Ekbom disease). Intravenous (IV) iron can rapidly reverse IDA and would be expected to similarly reverse RLS caused by IDA. This is the first consecutive case series evaluating the effects of IV iron therapy on RLS occurring with IDA (RLS-IDA). RLS-IDA patients were evaluated before and 7-12 months after a 1000-mg IV infusion of low-molecular-weight iron dextran (INFeD(@)) using validated questionnaires and standardized telephone interview. Patients were classified as respondent versus nonrespondent for RLS improvement. Follow-up data were obtained on 42 (70%) of 60 consecutive RLS-IDA patients. The symptoms of RLS were reduced in 76% (32/42) with 47% (20/42) showing an extended response lasting >6 months. The response did not relate to age or gender, but tended to be less among African-Americans than Whites (40% (2/5) vs. 81% (30/37), p = 0.078). White respondents versus nonrespondents had higher hemoglobin levels after treatment (12.1 vs. 11.3 g/dl, p = 0.03). RLS-IDA is reduced after administration of IV iron in most cases, but the 24% failing to respond was higher than expected. The nonrespondents all showed below-normal hemoglobin levels (<12.5 g/dl) suggesting a failure of adequate treatment of the iron deficiency. IV iron treatment of the RLS with IDA likely requires ensuring more than minimally adequate body iron stores to support iron delivery to the brain. For some, this may require a dose higher than the customary 1000-mg IV iron used for the treatment of either IDA or RLS alone. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease.

    PubMed

    Binley, Katie; Widdowson, Peter; Loader, Julie; Kelleher, Michelle; Iqball, Sharifah; Ferrige, Georgina; de Belin, Jackie; Carlucci, Marie; Angell-Manning, Diana; Hurst, Felicity; Ellis, Scott; Miskin, James; Fernandes, Alcides; Wong, Paul; Allikmets, Rando; Bergstrom, Christopher; Aaberg, Thomas; Yan, Jiong; Kong, Jian; Gouras, Peter; Prefontaine, Annick; Vezina, Mark; Bussieres, Martin; Naylor, Stuart; Mitrophanous, Kyriacos A

    2013-06-12

    StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration.

  17. Transduction of Photoreceptors With Equine Infectious Anemia Virus Lentiviral Vectors: Safety and Biodistribution of StarGen for Stargardt Disease

    PubMed Central

    Binley, Katie; Widdowson, Peter; Loader, Julie; Kelleher, Michelle; Iqball, Sharifah; Ferrige, Georgina; de Belin, Jackie; Carlucci, Marie; Angell-Manning, Diana; Hurst, Felicity; Ellis, Scott; Miskin, James; Fernandes, Alcides; Wong, Paul; Allikmets, Rando; Bergstrom, Christopher; Aaberg, Thomas; Yan, Jiong; Kong, Jian; Gouras, Peter; Prefontaine, Annick; Vezina, Mark; Bussieres, Martin; Naylor, Stuart; Mitrophanous, Kyriacos A.

    2013-01-01

    Purpose. StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. Methods. Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. Results. Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. Conclusions. In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration. PMID:23620430

  18. What Causes Aplastic Anemia?

    MedlinePlus

    ... to aplastic anemia. Examples include Fanconi anemia , Shwachman-Diamond syndrome, dyskeratosis (DIS-ker-ah-TO-sis) congenita, and Diamond-Blackfan anemia. Rate This Content: NEXT >> Featured Video ...

  19. Sickle cell anemia - resources

    MedlinePlus

    Resources - sickle cell anemia ... The following organizations are good resources for information on sickle cell anemia : American Sickle Cell Anemia Association -- www.ascaa.org National Heart, Blood, and Lung Institute -- www. ...

  20. Anemia (For Parents)

    MedlinePlus

    ... a drug or toxin. Anemia From Destruction of Red Blood Cells When the body destroys red blood cells (a ... but can affect all races. continue Anemia From Red Blood Cell Loss Blood loss can cause anemia — whether from ...

  1. Analysis of microsatellite polymorphism around the HLA-B locus in Iranian patients with Behçet's disease.

    PubMed

    Mizuki, N; Yabuki, K; Ota, M; Katsuyama, Y; Ando, H; Nomura, E; Funakoshi, K; Davatchi, F; Chams, H; Nikbin, B; Ghaderi, A A; Ohno, S; Inoko, H

    2002-11-01

    We have previously suggested that in a Japanese population the susceptible locus for Behçet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100 kb around the HLA-B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA-B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.

  2. Added value of hepcidin quantification for the diagnosis and follow-up of anemia-related diseases.

    PubMed

    Lefebvre, Thibaud; Lasocki, Sigismond; Fénéant-Thibault, Martine; Lamy, Pierre-Jean; Cunat, Séverine; Ropert-Bouchet, Madeleine; Aguilar-Martinez, Patricia; Lehmann, Sylvain; Delaby, Constance

    2017-02-01

    Iron homeostasis is based on a strict control of both intestinal iron absorption and iron recycling through reticulo-endothelial system. Hepcidin controls the iron fluxes in order to maintain sufficient iron levels for erythropoietic activities, hemoproteins synthesis or enzymes function, but also to limit its toxic accumulation throughout the body. Hepcidin expression is regulated by various stimuli: inflammation and iron stimulate the production of the peptide, while anemia, erythropoiesis and hypoxia repress its production. Regulation of hepcidin expression is not so simple in complex pathological situations such as hemolytic anemia, cancer or chronic inflammation. Serum hepcidin quantification in association with the diagnostic tests currently available is quite promising for the diagnosis or the follow-up of anemia in those conditions. This study is part of the working group « Clinical interests of hepcidin quantification » of the Société française de biologie clinique.

  3. Clinical impact of the ERBP Working Group 2010 Recommendations for the anemia management in chronic kidney disease not on dialysis: ACERCA study.

    PubMed

    Martínez-Castelao, Alberto; Cases, Aleix; Carballada, Alberto Torre; Iranzo, Javier Torralba; Bronsoms, Josep; Vallès-Prats, Martí; Monserrat, Daniel Torán; Jimenez, Elisabet Masso

    2015-01-01

    The Anemia Working Group of ERBP in 2010 recommended a target hemoglobin (Hb) level in the range of 11-12 g/dL, without intentionally exceeding 13 g/dL during the treatment with erythropoiesis stimulating agents (ESAs). This study evaluated if there was a clinical impact of this statement in the anemia management of chronic kidney disease (CKD) patients treated with ESAs not on dialysis in routine clinical practice in Spain. This was an observational and cross-sectional study carried out in CKD patients not on dialysis in Spain who initiated ESA treatment (naïve), or were shifted from a previous ESA to another ESAs (converted) since January 2011. Of 441 patients evaluated, 67.6% were naïve and 32.4% were converted. At the study visit, 42.5% of naïve patients achieved the Hb target of 11-12 g/dL, with a mean Hb of 11.3±1.3 g/dL (vs 10.1±0.9 g/dL at the start of ESA therapy). Only 35.3% of converted patients maintained Hb levels within the recommended target at the study visit. Yet, 8.2% of naïve patients and 7.9% of those converted had Hb levels >13 g/dL. Hb levels were similar across subgroups of patients, regardless of the presence of significant comorbidities. Anemia management in CKD patients treated with ESAs by Spanish nephrologists seems to be aimed at preventing Hb levels <11 g/dL, while <50% of patients were within the narrow recommended Hb target range. This, together with the lack of individualization in Hb targets according to patients' comorbidities show that there is still room for improvement in renal anemia management in the clinical setting. Copyright © 2015. Published by Elsevier España, S.L.U.

  4. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    PubMed Central

    Lee, Soo Min; Nguyen, Dara; Anand, Marie; Kant, Ritu; Köhncke, Clemens; Lisewski, Ulrike; Roepke, Torsten K.; Hu, Zhaoyang; Abbott, Geoffrey W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2─/─ mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis. PMID:26984260

  5. [Infectious complications after surgical splenectomy in children with sickle cell anemia disease].

    PubMed

    Monaco Junior, Cypriano Petrus; Fonseca, Patricia Belintani Blum; Braga, Josefina Aparecida Pellegrini

    2015-01-01

    To evaluate the frequency of infectious complications in children with sickle cell disease (SCD) after surgical splenectomy for acute splenic sequestration crisis. Retrospective cohort of children with SCD who were born after 2002 and were regularly monitored until July 2013. Patients were divided into two groups: cases (children with SCD who underwent surgical splenectomy after an episode of splenic sequestration) and controls (children with SCD who did not have splenic sequestration and surgical procedures), in order to compare the frequency of invasive infections (sepsis, meningitis, bacteremia with positive blood cultures, acute chest syndrome and/or pneumonia) by data collected from medical records. Data were analyzed by descriptive statistical analysis. 44 patients were included in the case group. The mean age at the time of splenectomy was 2.6 years (1-6.9 years) and the mean postoperative length of follow-up was 6.1 years (3.8-9.9 years). The control group consisted of 69 patients with a mean age at the initial follow-up visit of 5.6 months (1-49 months) and a mean length of follow-up of 7.2 years (4-10.3 years). All children received pneumococcal conjugate vaccine. No significant difference was observed between groups in relation to infections during the follow-up. Surgical splenectomy in children with sickle cell disease that had splenic sequestration did not affect the frequency of infectious complications during 6 years of clinical follow-up. Copyright © 2015 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  6. Iron refractory iron deficiency anemia

    PubMed Central

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  7. Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients

    PubMed Central

    Saadah, Omar I.; Shaik, Noor Ahmad; Banaganapalli, Babajan; Salama, Mohammed A.; Al-Harthi, Sameer E.; Wang, Jun; Shawoosh, Harbi A.; Alghamdi, Sharifa A.; Bin-Taleb, Yagoub Y.; Alhussaini, Bakr H.; Elango, Ramu; Al-Aama, Jumana Y.

    2015-01-01

    Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22–5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05–2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17–0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD. PMID:26843707

  8. [Pernicious anemia in an adolescent with type 1 diabetes mellitus].

    PubMed

    Carneiro, M; Dumont, C

    2009-04-01

    The most frequent organ-specific autoimmune diseases associated with type 1 diabetes mellitus in children are hypothyroidism and celiac disease. Among adults, other associations exist, notably with pernicious anemia, which is extremely rare in children. We relate the observation of an adolescent with type 1 diabetes mellitus and hypothyroidism, admitted for severe anemia in addition to chronic anemia caused by autoimmune gastritis. Blood cell count showed severe aregenerative anemia with pancytopenia, with signs of non-autoimmune hemolysis. Vitamin B12 levels were low, bone marrow aspiration revealed erythroid hyperplasia, and anti-intrinsic factor antibodies were positive, providing the diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 produced brisk reticulosis after 6 days, with a subsequent rapid resolution of the anemia. Follow-up of type 1 diabetes mellitus in children requires screening for organ-specific autoimmune diseases; in case of unexplained anemia, autoimmune gastritis must be suggested. It can evolve into pernicious anemia.

  9. Parenteral iron compounds: potent oxidants but mainstays of anemia management in chronic renal disease.

    PubMed

    Zager, Richard A

    2006-09-01

    Ferric iron (Fe)-carbohydrate complexes are widely used for treating Fe deficiency in patients who are unable to meet their Fe requirements with oral supplements. Intravenous Fe generally is well tolerated and effective in correcting Fe-deficient states. However, the complexing of Fe to carbohydrate polymers does not block its potent pro-oxidant effects; systemic free radical generation and, possibly, tissue damage may result. The purpose of this review is to (1) underscore the capacity of currently used parenteral Fe formulations to induce oxidative stress, (2) compare the severity of these oxidant reactions with those that result from unshielded Fe salts and with each other, and (3) speculate as to the potential of these agents to induce acute renal cell injury and augment systemic inflammatory responses. The experimental data that are reviewed should not be extrapolated to the clinical setting or be used for clinical decision making. Rather, it is hoped that the information provided herein may have utility for clinical hypothesis generation and, hence, future clinical studies. By so doing, a better understanding of Fe's potential protean effects on patients with renal disease may result.

  10. Multi-locus genetic risk score predicts risk for Crohn’s disease in Slovenian population

    PubMed Central

    Zupančič, Katarina; Skok, Kristijan; Repnik, Katja; Weersma, Rinse K; Potočnik, Uroš; Skok, Pavel

    2016-01-01

    AIM: To develop a risk model for Crohn’s disease (CD) based on homogeneous population. METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group. RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS > 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76. CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population. PMID:27076762

  11. Multi-locus genetic risk score predicts risk for Crohn's disease in Slovenian population.

    PubMed

    Zupančič, Katarina; Skok, Kristijan; Repnik, Katja; Weersma, Rinse K; Potočnik, Uroš; Skok, Pavel

    2016-04-14

    To develop a risk model for Crohn's disease (CD) based on homogeneous population. In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group. The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS > 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76. The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population.

  12. Alterations of the IKBKG locus and diseases: an update and a report of 13 novel mutations.

    PubMed

    Fusco, Francesca; Pescatore, Alessandra; Bal, Elodie; Ghoul, Aida; Paciolla, Mariateresa; Lioi, Maria Brigida; D'Urso, Michele; Rabia, Smail Hadj; Bodemer, Christine; Bonnefont, Jean Paul; Munnich, Arnold; Miano, Maria Giuseppina; Smahi, Asma; Ursini, Matilde Valeria

    2008-05-01

    Mutations in the inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), also called nuclear factor-kappaB (NF-kB) essential modulator (NEMO), gene are the most common single cause of incontinentia pigmenti (IP) in females and anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males. The IKBKG gene, located in the Xq28 chromosomal region, encodes for the regulatory subunit of the inhibitor of kappaB (IkB) kinase (IKK) complex required for the activation of the NF-kB pathway. Therefore, the remarkably heterogeneous and often severe clinical presentation reported in IP is due to the pleiotropic role of this signaling transcription pathway. A recurrent exon 4_10 genomic rearrangement in the IKBKG gene accounts for 60 to 80% of IP-causing mutations. Besides the IKBKG rearrangement found in IP females (which is lethal in males), a total of 69 different small mutations (missense, frameshift, nonsense, and splice-site mutations) have been reported, including 13 novel ones in this work. The updated distribution of all the IP- and EDA-ID-causing mutations along the IKBKG gene highlights a secondary hotspot mutation in exon 10, which contains only 11% of the protein. Furthermore, familial inheritance analysis revealed an unexpectedly high incidence of sporadic cases (>65%). The sum of the observations can aid both in determining the molecular basis of IP and EDA-ID allelic diseases, and in genetic counseling in affected families.

  13. Renoprotective effect of renin-angiotensin-aldosterone system blockade in patients with predialysis advanced chronic kidney disease, hypertension, and anemia.

    PubMed

    Hsu, Ta-Wei; Liu, Jia-Sin; Hung, Szu-Chun; Kuo, Ko-Lin; Chang, Yu-Kang; Chen, Yu-Chi; Hsu, Chih-Cheng; Tarng, Der-Cherng

    2014-03-01

    The benefit of using a renin-angiotensin-aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined. To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia. DESIGN Prospective cohort study. Taiwan. From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesis-stimulating agents. Users (n = 14,117) and nonusers (n = 14,380) of ACEIs/ARBs. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers. In a median follow-up of 7 months, 20,152 patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progression to end-stage renal disease requiring dialysis. Use of ACEIs/ARBs was associated with a lower risk for long-term dialysis (HR, 0.94 [95% CI, 0.91-0.97]) and the composite outcome of long-term dialysis or death (0.94 [0.92-0.97]). The renal benefit of ACEI/ARB use was consistent across most patient subgroups, as was that of ACEI or ARB monotherapy. Compared with nonusers, the ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk of predialysis mortality caused by hyperkalemia was not significantly increased (HR, 1.03 [95% CI, 0.92-1.16]; P = .30). Patients with stable hypertension and advanced CKD who receive therapy with ACEIs/ARBs exhibit an association with lower risk for long-term dialysis or death by 6%. This benefit does not increase the risk of all-cause mortality.

  14. RPS2, an Arabidopsis disease resistance locus specifying recognition of Pseudomonas syringae strains expressing the avirulence gene avrRpt2.

    PubMed Central

    Kunkel, B N; Bent, A F; Dahlbeck, D; Innes, R W; Staskawicz, B J

    1993-01-01

    A molecular genetic approach was used to identify and characterize plant genes that control bacterial disease resistance in Arabidopsis. A screen for mutants with altered resistance to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst) expressing the avirulence gene avrRpt2 resulted in the isolation of four susceptible rps (resistance to P. syringae) mutants. The rps mutants lost resistance specifically to bacterial strains expressing avrRpt2 as they retained resistance to Pst strains expressing the avirulence genes avrB or avrRpm1. Genetic analysis indicated that in each of the four rps mutants, susceptibility was due to a single mutation mapping to the same locus on chromosome 4. Identification of a resistance locus with specificity for a single bacterial avirulence gene suggests that this locus, designated RPS2, controls specific recognition of bacteria expressing the avirulence gene avrRpt2. Ecotype Wü-0, a naturally occurring line that is susceptible to Pst strains expressing avrRpt2, appears to lack a functional allele at RPS2, demonstrating that there is natural variation at the RPS2 locus among wild populations of Arabidopsis. PMID:8400869

  15. Independent and population-specific association of risk variants at the IRGM locus with Crohn's disease

    PubMed Central

    Prescott, Natalie J.; Dominy, Katherine M.; Kubo, Michiaki; Lewis, Cathryn M.; Fisher, Sheila A.; Redon, Richard; Huang, Ni; Stranger, Barbara E.; Blaszczyk, Katarzyna; Hudspith, Barry; Parkes, Gareth; Hosono, Naoya; Yamazaki, Keiko; Onnie, Clive M.; Forbes, Alastair; Dermitzakis, Emmanouil T.; Nakamura, Yusuke; Mansfield, John C.; Sanderson, Jeremy; Hurles, Matthew E.; Roberts, Roland G.; Mathew, Christopher G.

    2010-01-01

    DNA polymorphisms in a region on chromosome 5q33.1 which contains two genes, immunity related GTPase related family, M (IRGM) and zinc finger protein 300 (ZNF300), are associated with Crohn's disease (CD). The deleted allele of a 20 kb copy number variation (CNV) upstream of IRGM was recently shown to be in strong linkage disequilibrium (LD) with the CD-associated single nucleotide polymorphisms and is itself associated with CD (P < 0.01). The deletion was correlated with increased or reduced expression of IRGM in transformed cells in a cell line-dependent manner, and has been proposed as a likely causal variant. We report here that small insertion/deletion polymorphisms in the promoter and 5′ untranslated region of IRGM are, together with the CNV, strongly associated with CD (P = 1.37 × 10−5 to 1.40 × 10−9), and that the CNV and the 5′-untranslated region variant −308(GTTT)5 contribute independently to CD susceptibility (P = 2.6 × 10−7 and P = 2 × 10−5, respectively). We also show that the CD risk haplotype is associated with a significant decrease in IRGM expression (P < 10−12) in untransformed lymphocytes from CD patients. Further analysis of these variants in a Japanese CD case–control sample and of IRGM expression in HapMap populations revealed that neither the IRGM insertion/deletion polymorphisms nor the CNV was associated with CD or with altered IRGM expression in the Asian population. This suggests that the involvement of the IRGM risk haplotype in the pathogenesis of CD requires gene–gene or gene–environment interactions which are absent in Asian populations, or that none of the variants analysed are causal, and that the true causal variants arose after the European–Asian split. PMID:20106866

  16. Further refinement of the locus for Machado-Joseph disease (MJD) gene

    SciTech Connect

    Endo, K.; Tanaka, H.; Takiyama, Y.

    1994-09-01

    Machado-Joseph disease (MJD) is an autosomal dominant, multi-system, neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. We have discovered that the gene for MJD is mapped to chromosome 14q24.3-32.1 in a region of 29 cM between D14S53 and D14S45 using 7 microsatellite DNA markers. To further characterize the candidate region for MJD gene, we analyzed 80 individuals including 35 affected members from 5 Japanese MJD families (3 families are pathologically proven and 2 families are diagnosed based on the clinical manifestations), using 10 new microsatellite DNA markers (D14S76, D14S61, D14S59, D14S67, D14S291, D14S280, D14S81, D14S265, D14S62, and D14S65) in the region defined by previous linkage analysis. High lod scores of 9.227, 3.5207, 9.0320, and 6.7032 were obtained at D14S48, D14S291, D14S280, and D14S81 at recombination fractions of 0.00, 0.05, 0.01, and 0.05, respectively. We have observed recombination events at D14S291 and D14S81 in affected individuals while no recombination events were observed at D14S280. The results indicate that the gene for MJD is likely to be located in the region of 4CM between D14S291 and D14S81. The identification of multiple informative flanking markers should facilitate positional cloning of the gene for MJD.

  17. SOX10 regulates an alternative promoter at the Charcot-Marie-Tooth disease locus MTMR2.

    PubMed

    Fogarty, Elizabeth A; Brewer, Megan H; Rodriguez-Molina, Jose F; Law, William D; Ma, Ki H; Steinberg, Noah M; Svaren, John; Antonellis, Anthony

    2016-09-15

    Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function. Loss-of-function mutations in the gene encoding myotubularin-related protein 2 (MTMR2) cause Charcot-Marie-Tooth disease type 4B1 (CMT4B1), a severe demyelinating peripheral neuropathy characterized by myelin outfoldings along peripheral nerves. Previous reports indicate that MTMR2 is ubiquitously expressed making it unclear how loss of this gene causes a Schwann cell-specific phenotype. To address this, we performed computational and functional analyses at MTMR2 to identify transcriptional regulatory elements important for Schwann cell expression. Through these efforts, we identified an alternative, SOX10-responsive promoter at MTMR2 that displays strong regulatory activity in immortalized rat Schwann (S16) cells. This promoter directs transcription of a previously unidentified MTMR2 transcript that is enriched in mouse Schwann cells compared to immortalized mouse motor neurons (MN-1), and is predicted to encode an N-terminally truncated protein isoform. The expression of the endogenous transcript is induced in a heterologous cell line by ectopically expressing SOX10, and is nearly ablated in Schwann cells by impairing SOX10 function. Intriguingly, overexpressing the two MTMR2 protein isoforms in HeLa cells revealed that both localize to nuclear puncta and the shorter isoform displays higher nuclear localization compared to the longer isoform. Combined, our data warrant further investigation of the truncated MTMR2 protein isoform in Schwann cells and in CMT4B1 pathogenesis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Classification of anemia for gastroenterologists

    PubMed Central

    Moreno Chulilla, Jose Antonio; Romero Colás, Maria Soledad; Gutiérrez Martín, Martín

    2009-01-01

    Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia, its morphological classification (microcytic, macrocytic and normocytic) and pathogenic classification (regenerative and hypo regenerative), and integration of these classifications. Interpretation of laboratory tests is included, from the simplest (blood count, routine biochemistry) to the more specific (iron metabolism, vitamin B12, folic acid, reticulocytes, erythropoietin, bone marrow examination and Schilling test). In the text and various algorithms, we propose a hierarchical and logical way to reach a diagnosis as quickly as possible, by properly managing the medical interview, physical examination, appropriate laboratory tests, bone marrow examination, and other complementary tests. The prevalence is emphasized in all sections so that the gastroenterologist can direct the diagnosis to the most common diseases, although the tables also include rare diseases. Digestive diseases potentially causing anemia have been studied in preference, but other causes of anemia have been included in the text and tables. Primitive hematological diseases that cause anemia are only listed, but are not discussed in depth. The last section is dedicated to simplifying all items discussed above, using practical rules to guide diagnosis and medical care with the greatest economy of resources and time. PMID:19787825

  19. Crohn's Disease Risk Alleles on the NOD2 Locus Have Been Maintained by Natural Selection on Standing Variation

    PubMed Central

    Nakagome, Shigeki; Mano, Shuhei; Kozlowski, Lukasz; Bujnicki, Janusz M.; Shibata, Hiroki; Fukumaki, Yasuaki; Kidd, Judith R.; Kidd, Kenneth K.; Kawamura, Shoji; Oota, Hiroki

    2012-01-01

    Risk alleles for complex diseases are widely spread throughout human populations. However, little is known about the geographic distribution and frequencies of risk alleles, which may contribute to differences in disease susceptibility and prevalence among populations. Here, we focus on Crohn's disease (CD) as a model for the evolutionary study of complex disease alleles. Recent genome-wide association studies and classical linkage analyses have identified more than 70 susceptible genomic regions for CD in Europeans, but only a few have been confirmed in non-European populations. Our analysis of eight European-specific susceptibility genes using HapMap data shows that at the NOD2 locus the CD-risk alleles are linked with a haplotype specific to CEU at a frequency that is significantly higher compared with the entire genome. We subsequently examined nine global populations and found that the CD-risk alleles spread through hitchhiking with a high-frequency haplotype (H1) exclusive to Europeans. To examine the neutrality of NOD2, we performed phylogenetic network analyses, coalescent simulation, protein structural prediction, characterization of mutation patterns, and estimations of population growth and time to most recent common ancestor (TMRCA). We found that while H1 was significantly prevalent in European populations, the H1 TMRCA predated human migration out of Africa. H1 is likely to have undergone negative selection because 1) the root of H1 genealogy is defined by a preexisting amino acid substitution that causes serious conformational changes to the NOD2 protein, 2) the haplotype has almost become extinct in Africa, and 3) the haplotype has not been affected by the recent European expansion reflected in the other haplotypes. Nevertheless, H1 has survived in European populations, suggesting that the haplotype is advantageous to this group. We propose that several CD-risk alleles, which destabilize and disrupt the NOD2 protein, have been maintained by natural

  20. Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal Dialysis

    PubMed Central

    Zabaneh, Raja; Roger, Simon D.; El-Shahawy, Mohamed; Roppolo, Michael; Runyan, Grant; O'Neil, Janet; Qiu, Ping

    2015-01-01

    ♦ Background: Peginesatide is a novel, synthetic, peptide-based pegylated erythropoiesis-stimulating agent that is designed specifically to stimulate the erythropoietin receptor. The purpose of the present study was to assess, for the first time, the efficacy and safety of peginesatide in chronic kidney disease (CKD) patients receiving peritoneal dialysis (PD) and previously on epoetin treatment. ♦ Methods: In this open-label multicenter study, 59 PD patients with CKD were converted from epoetin (alfa or beta) to once-monthly peginesatide. Doses were titrated to maintain hemoglobin levels between 10 g/dL and 12 g/dL during the 25 weeks of the study. The primary endpoint was change from baseline in mean hemoglobin values during the evaluation period (weeks 20 – 25). ♦ Results: The mean hemoglobin value during the evaluation period was 11.3 ± 1.07 g/dL, and the mean change from baseline was 0.10 ± 1.15 g/dL (95% confidence limits: −0.24, 0.44 g/dL). During the evaluation period, most patients maintained hemoglobin levels between 10 g/dL and 12 g/dL (63.0%) and within ±1.0 g/dL of baseline (60.9%). The median weekly epoetin dose at baseline was 96.0 U/kg, and the median starting peginesatide dose was 0.047 mg/kg. Forty-three patients (72.9%) completed the study. Six patients (10.2%) received red blood cell transfusions. The observed adverse event profile was consistent with underlying conditions in the PD patient population. The most common adverse event was peritonitis (20.3%), a complication commonly associated with PD. Four deaths occurred during the study (2 related to septic shock, and 1 each to myocardial ischemia and myasthenia gravis). ♦ Conclusions: In this study, once-monthly peginesatide maintained hemoglobin levels in PD patients after conversion from epoetin. PMID:24584613

  1. Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation.

    PubMed Central

    Cuppens, H; Lin, W; Jaspers, M; Costes, B; Teng, H; Vankeerberghen, A; Jorissen, M; Droogmans, G; Reynaert, I; Goossens, M; Nilius, B; Cassiman, J J

    1998-01-01

    In congenital bilateral absence of the vas deferens patients, the T5 allele at the polymorphic Tn locus in the CFTR (cystic fibrosis transmembrane conductance regulator) gene is a frequent disease mutation with incomplete penetrance. This T5 allele will result in a high proportion of CFTR transcripts that lack exon 9, whose translation products will not contribute to apical chloride channel activity. Besides the polymorphic Tn locus, more than 120 polymorphisms have been described in the CFTR gene. We hypothesized that the combination of particular alleles at several polymorphic loci might result in less functional or even insufficient CFTR protein. Analysis of three polymorphic loci with frequent alleles in the general population showed that, in addition to the known effect of the Tn locus, the quantity and quality of CFTR transcripts and/or proteins was affected by two other polymorphic loci: (TG)m and M470V. On a T7 background, the (TG)11 allele gave a 2.8-fold increase in the proportion of CFTR transcripts that lacked exon 9, and (TG)12 gave a sixfold increase, compared with the (TG)10 allele. T5 CFTR genes derived from patients were found to carry a high number of TG repeats, while T5 CFTR genes derived from healthy CF fathers harbored a low number of TG repeats. Moreover, it was found that M470 CFTR proteins matured more slowly, and that they had a 1.7-fold increased intrinsic chloride channel activity compared with V470 CFTR proteins, suggesting that the M470V locus might also play a role in the partial penetrance of T5 as a disease mutation. Such polyvariant mutant genes could explain why apparently normal CFTR genes cause disease. Moreover, they might be responsible for variation in the phenotypic expression of CFTR mutations, and be of relevance in other genetic diseases. PMID:9435322

  2. Thiamine-responsive megaloblastic anemia syndrome.

    PubMed

    Bay, Ali; Keskin, Mehmet; Hizli, Samil; Uygun, Hatice; Dai, Alper; Gumruk, Fatma

    2010-10-01

    Thiamine-responsive megaloblastic anemia (TRMA) syndrome usually associated with diabetes mellitus, anemia and deafness, due to mutations in SLC19A2, encoding a thiamine transporter protein. The onset of disease is usually seen during infancy or at early childhood and most of the TRMA patients are originated from consanguineous families. In this case, we report a 5-month-old boy who had diagnosis of TRMA during evaluations for his anemia and thrombocytopenia. The diagnosis of TRMA should be kept in mind in differential diagnosis of megaloblastic anemia especially in the populations where the consanguinity is frequent.

  3. Genetic correction of sickle cell anemia and beta-thalassemia: progress and new perspective.

    PubMed

    Perumbeti, Ajay; Malik, Punam

    2010-04-13

    Gene therapy for beta-globinopathies, particularly Beta-thalassemia and sickle cell anemia, holds promise for the future as a definitive corrective approach for these common and debilitating disorders. Correction of the beta-globinopathies using lentivirus vectors carrying the beta- or y-globin genes and elements of the locus control region has now been well established in murine models, and an understanding of "what is required to cure these diseases" has been developed in the first decade of the 21st century. A clinical trial using one such vector has been initiated in France with intriguing results, while other trials are under development. Vector improvements to enhance the safety and efficiency of lentivirus vectors are being explored, while new strategies, including homologous recombination in induced pluripotent cells, for correction of sickle cell anemia have shown proof-of-concept in vitro. Here, a review is provided of the current substantial progress in genetic correction of beta-globin disorders.

  4. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    PubMed Central

    Mealey, Robert H.; Zhang, Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.

    2012-01-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined. PMID:12954220

  5. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus.

    PubMed

    Mealey, Robert H; Zhang, Baoshan; Leib, Steven R; Littke, Matt H; McGuire, Travis C

    2003-09-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined.

  6. Chicken anemia virus and infectious bursal disease virus interfere with transcription of chicken IFN-alpha and IFN-gamma mRNA.

    PubMed

    Ragland, William L; Novak, Renata; El-Attrache, John; Savić, Vladimir; Ester, Katja

    2002-04-01

    Chicken anemia virus (CAV) and infectious bursal disease virus (IBDV) are the two most important viruses that cause immunosuppression in commercial chickens. Because inapparent, subclinical infections by these viruses cause immunosuppression, there is need for assessment of the immune status of chickens. Interference with induction of transcription for chicken interferon-alpha (ChIFN-alpha) and ChIFN-gamma was noted after subclinical infections with either CAV or IBDV. Because the immunosuppressive viruses of chickens may interfere with transcription for ChIFN-alpha and ChIFN-gamma, we propose using this interference to assess the immune status of chickens.

  7. Warm autoimmune hemolytic anemia.

    PubMed

    Naik, Rakhi

    2015-06-01

    Warm autoimmune hemolytic anemia (AIHA) is defined as the destruction of circulating red blood cells (RBCs) in the setting of anti-RBC autoantibodies that optimally react at 37°C. The pathophysiology of disease involves phagocytosis of autoantibody-coated RBCs in the spleen and complement-mediated hemolysis. Thus far, treatment is aimed at decreasing autoantibody production with immunosuppression or reducing phagocytosis of affected cells in the spleen. The role of complement inhibitors in warm AIHA has not been explored. This article addresses the diagnosis, etiology, and treatment of warm AIHA and highlights the role of complement in disease pathology.

  8. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

    PubMed Central

    Lambert, J-C; Grenier-Boley, B; Harold, D; Zelenika, D; Chouraki, V; Kamatani, Y; Sleegers, K; Ikram, M A; Hiltunen, M; Reitz, C; Mateo, I; Feulner, T; Bullido, M; Galimberti, D; Concari, L; Alvarez, V; Sims, R; Gerrish, A; Chapman, J; Deniz-Naranjo, C; Solfrizzi, V; Sorbi, S; Arosio, B; Spalletta, G; Siciliano, G; Epelbaum, J; Hannequin, D; Dartigues, J-F; Tzourio, C; Berr, C; Schrijvers, E M C; Rogers, R; Tosto, G; Pasquier, F; Bettens, K; Van Cauwenberghe, C; Fratiglioni, L; Graff, C; Delepine, M; Ferri, R; Reynolds, C A; Lannfelt, L; Ingelsson, M; Prince, J A; Chillotti, C; Pilotto, A; Seripa, D; Boland, A; Mancuso, M; Bossù, P; Annoni, G; Nacmias, B; Bosco, P; Panza, F; Sanchez-Garcia, F; Del Zompo, M; Coto, E; Owen, M; O'Donovan, M; Valdivieso, F; Caffara, P; Scarpini, E; Combarros, O; Buée, L; Campion, D; Soininen, H; Breteler, M; Riemenschneider, M; Van Broeckhoven, C; Alpérovitch, A; Lathrop, M; Trégouët, D-A; Williams, J; Amouyel, P

    2013-01-01

    Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case–control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43–1.96); P=1.1 × 10−10). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10−7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD. PMID:22430674

  9. Association of haplotypes of the TLR8 locus with susceptibility to Crohn's and Behçet's diseases.

    PubMed

    Ortiz-Fernández, Lourdes; García-Lozano, José-Raúl; Montes-Cano, Marco-Antonio; Conde-Jaldón, Marta; Leo, Eduardo; Ortego-Centeno, Norberto; Gómez-García, María; García-Hernández, Francisco-José; Márquez, José-Luis; Espinosa, Gerard; Graña-Gil, Genaro; Sánchez-Bursón, Juan; Juliá, María-Rosa; Blanco, Ricardo; Barnosi-Marín, Ana-Celia; Solans, Roser; Fanlo, Patricia; Rodríguez-Carballeira, Mónica; Camps, Teresa; Castañeda, Santos; Martín, Javier; González-Escribano, María-Francisca

    2015-01-01

    The aim of this study was to investigate the role of the TLR8, a mediator of innate inflammatory response, in susceptibility to two immune-mediated disorders characterised by dysregulation of the immune response, Crohn's and Behçet's diseases (CD and BD). A total of 844 CD, 371 BD patients and 1385 controls were genotyped in 8 tag single nucleotide polymorphisms (tSNPs) in the locus TLR8 (chromosome X). All these tSNPs have a minor allele frequency greater than 0.05 in the Caucasian population. The rs2407992 and the rs5744067 were associated with susceptibility to BD and CD, respectively (OR=1.34, 95%CI=1.10-1.62, p=0.0025 and OR=0.82, 95%CI=0.68-0.99, p=0.045, respectively). Although after stratification by gender, statistically significant differences in the distribution of the aforementioned SNPs were only observed in the females groups (BD OR=1.31, 95%CI=1.06-1.64, p=0.012 and CD OR=0.84, 95%CI=0.72-0.98, p=0.044) the trend was similar among males. Since the rs5744067 and rs2407992 are located in the same linkage disequilibrium block, we performed a haplotypic analysis by combination of the tSNPs. One haplotype (H1) was identified as a protective factor in BD (OR=0.75, 95%CI=0.62-0.90, p=0.0027) and another (H2) as a protective factor in CD (OR=0.78, 95%CI=0.64-094, p=0.0102). No statistically significant differences in the mean of the levels of expression attributable to the haplotype variants were found in the in silico analysis performed. Our results suggest a relationship between the TLR8 and the susceptibility to CD and BD. Nevertheless, these differences could not be imputed to the levels of expression.

  10. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses...

  11. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses of...

  12. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses of...

  13. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses of...

  14. Case 40. Misdiagnosis of refractory macrocytic anemia.

    PubMed

    Stringaris, Kate; Bain, Barbara

    2008-11-01

    A diagnosis of myelodysplastic syndrome, refractory anemia subtype, was made in an elderly Indian woman on the basis of a refractory macrocytic anemia with normal vitamin B(12) and folate assays, normal thyroid function, essentially normal liver function and normal cytogenetic analysis. Disease evolution revealed that the diagnosis was erroneous.

  15. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses of...

  16. Anti-hepcidin therapy for iron-restricted anemias.

    PubMed

    Nemeth, Elizabeta

    2013-10-24

    In this issue of Blood, Cooke et al demonstrate the potential of a fully human anti-hepcidin antibody as a novel therapeutic for iron-restricted anemias such as anemia of inflammation, cancer, or chronic kidney disease (formerly known as “anemia of chronic diseases”).

  17. [Anemia: guidelines comparison].

    PubMed

    Del Vecchio, Lucia

    2009-01-01

    The development of recombinant human erythropoietin and its introduction into the market in the late 1980s has significantly improved the quality of life of patients with chronic kidney disease (CKD) and reduced the need for blood transfusions. Starting from a cautious target, a progressive increase in the recommended hemoglobin levels has been observed over the years, in parallel with an increase in the obtained levels. This trend has gone together with the publication of findings of observational studies showing a relationship between the increase in hemoglobin levels and a reduction in the mortality risk, with the conduction of clinical trials testing the effects of complete anemia correction, and with the compilation of guidelines on anemia control in CKD patients by scientific societies and organizations. In the last two years, evidence of a possible increase in the mortality risk in those patients who were randomized to high hemoglobin levels has resulted in a decrease in the upper limit of the recommended Hb target to be obtained with erythropoietin stimulating agents (ESA), and consequently in a narrowing of the target range. Comparison of guidelines on anemia control in CKD patients is an interesting starting point to discuss single recommendations, strengthen their importance, or suggest new topics of research to fill up important gaps in knowledge.

  18. Anemia of chronic disease

    MedlinePlus

    ... Benz EJ Jr, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice . 6th ed. Philadelphia, PA: ... 2/1/2016 Updated by: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. ...

  19. Reticulocytosis and anemia are associated with an increased risk of death and stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease.

    PubMed

    Meier, Emily Riehm; Wright, Elizabeth C; Miller, Jeffery L

    2014-09-01

    Prior analyses of the Cooperative Study of Sickle Cell Disease (CSSCD) newborn cohort identified elevated white blood cell (WBC) count, low baseline hemoglobin and dactylitis between the ages of 1 and 2 years as markers of severe disease. Reticulocytosis was also associated with severe disease. Here, we further analyzed data collected on enrolled CSSCD infants for the predictive value of those markers for stroke and death later in life. Three hundred fifty-four CSSCD subjects were identified who had absolute reticulocyte counts (ARC) measured during infancy (2 to 6 months of age). Infants with higher ARC had significantly increased risk of stroke or death during childhood; lower hemoglobin levels also increased the risk but to a lesser degree than ARC. WBC levels and dactylitis were not predictive of death or stroke. These data suggest that reticulocytosis among asymptomatic infants with sickle cell anemia is associated with an increased risk of death or stroke during childhood.

  20. Soluble transferrin receptor and transferrin receptor-ferritin index in iron deficiency anemia and anemia in rheumatoid arthritis.

    PubMed

    Margetic, Sandra; Topic, Elizabeta; Ruzic, Dragica Ferenec; Kvaternik, Marina

    2005-01-01

    The aim of the study was to evaluate the clinical efficiency of soluble transferrin receptor and transferrin receptor-ferritin index (sTfR/logF) in the diagnosis of iron deficiency anemia, as well as the differential diagnosis of iron deficiency anemia and anemia in rheumatoid arthritis. The study included 96 patients with anemia and 61 healthy volunteers as a control group. In healthy subjects there were no significant sex and age differences in the parameters tested. The study results showed these parameters to be reliable in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis of iron deficiency anemia and anemia of chronic disease. The results indicate that sTfR/logF could be used to help differentiate coexisting iron deficiency in patients with anemia of chronic disease. Receiver operating characteristic analysis showed a higher discriminating power of transferrin receptor-ferritin index vs. soluble transferrin receptor in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis between iron deficiency anemia and anemia of chronic disease. In patients with anemia in rheumatoid arthritis, the parameters tested showed no significant differences with respect to C-reactive protein concentration. These results suggested that the parameters tested are not affected by acute or chronic inflammatory disease.

  1. Iron deficiency anemia in children.

    PubMed

    Subramaniam, Girish; Girish, Meenakshi

    2015-06-01

    Iron deficiency is not just anemia; it can be responsible for a long list of other manifestations. This topic is of great importance, especially in infancy and early childhood, for a variety of reasons. Firstly, iron need is maximum in this period. Secondly, diet in infancy is usually deficient in iron. Thirdly and most importantly, iron deficiency at this age can result in neurodevelopmental and cognitive deficits, which may not be reversible. Hypochromia and microcytosis in a complete blood count (CBC) makes iron deficiency anemia (IDA) most likely diagnosis. Absence of response to iron should make us look for other differential diagnosis like β thalassemia trait and anemia of chronic disease. Celiac disease is the most important cause of true IDA not responding to oral iron therapy. While oral ferrous sulphate is the cheapest and most effective therapy for IDA, simple nonpharmacological and pharmacological measures can go a long way in prevention of iron deficiency.

  2. Two-stage association study in Chinese Han identifies two independent associations in CCR1/CCR3 locus as candidate for Behçet's disease susceptibility.

    PubMed

    Hou, Shengping; Xiao, Xiang; Li, Fuzhen; Jiang, Zhengxuan; Kijlstra, Aize; Yang, Peizeng

    2012-12-01

    Previous GWAS studies from Turkey suggested a potential risk locus at CCR1/CCR3 for Behçet's disease. However, this locus did not reach the GWAS significance threshold and has not yet been examined in other ethnic populations. The current study aimed to explore whether this locus was associated with Behçet's disease in Chinese Han and the functional role of the identified variants. A two-stage association study was performed in 653 patients and 1,685 controls using the iPLEX system. Real-time PCR was performed to examine the expression level of CCR1 and CCR3 genes. Haplotype analysis was used to construct the haplotype block. Logistic regression analysis was applied to calculate the independence of multiple associations. Bonferroni correction was applied to account for multiple testing. First stage analysis showed that ten SNPs, located in 3'UTR, 5'UTR in CCR1 or 5'UTR in CCR3, were significantly associated with Behçet's disease (P(c) = 0.018 to 1.3 × 10(-3)). The associations of six SNPs within this locus are independent after control for the genetic effect of rs17282391 using logistic regression analysis. Haplotype analysis identified three associated haplotypes: H3 (GTGAC), H6 (CCATTA) and H9 (CGA) (P(c) = 0.04 to 7.79 × 10(-4)). Three SNPs rs13084057, rs13092160 and rs13075270 showed consistent association in replication and combining studies (replication P(c) = 5.31 × 10(-5) to 1.44 × 10(-5); combining P(c) = 2.76 × 10(-7) to 6.50 × 10(-8)). Interestingly, eQTLs database reveals that SNP rs13092160 is eQTLs SNP, suggesting that this SNP is likely to be functional SNP that directly affects gene expression. The expression of CCR1 and CCR3 was increased in individuals with the CT genotype of rs13092160 (P < 0.05). No significant difference was found for the mRNA level of CCR1 and CCR3 between Behçet's patients and controls. These findings strongly indicate CCR1/CCR3 as a novel locus underlying Behçet's disease.

  3. Quantitation of Marek's disease and chicken anemia viruses in organs of experimentally infected chickens and commercial chickens by multiplex real-time PCR.

    PubMed

    Davidson, Irit; Raibshtein, I; Al-Touri, A

    2013-06-01

    The worldwide distribution of chicken anemia virus (CAV) and Marek's disease virus (MDV) is well documented. In addition to their economic significance in single- or dual-virus infections, the two viruses can often accompany various other pathogens and affect poultry health either directly, by causing tumors, anemia, and delayed growth, or indirectly, by aggravating other diseases, as a result of their immunosuppressive effects. After a decade of employing the molecular diagnosis of those viruses, which replaced conventional virus isolation, we present the development of a real-time multiplex PCR for the simultaneous detection of both viruses. The real-time PCRs for MDV and for CAV alone are more sensitive than the respective end-point PCRs. In addition, the multiplex real-time shows a similar sensitivity when compared to the single real-time PCR for each virus. The newly developed real-time multiplex PCR is of importance in terms of the diagnosis and detection of low copies of each virus, MDV and CAV in single- and in multiple-virus infections, and its applicability will be further evaluated.

  4. [Anemia in patients with rheumatoid arthritis].

    PubMed

    Wahle, M

    2012-12-01

    One of the most frequent extra-articular organ manifestations in rheumatoid arthritis (RA) is anemia. As anemia in RA patients may result in severe symptoms and aggravation of other disease manifestations (e.g. arteriosclerosis), the influence on the course of RA is profound. However, the importance of anemia in RA patients is frequently underestimated. The etiology of anemia in RA is complex. Anemia of inflammation (AI) and iron deficiency anemia, alone or in combination are the most frequent forms of anemia in RA. Changes in iron metabolism are the leading causes of anemia in RA patients and mainly induced by the altered synthesis and function of hepcidin and ferroportin. Hepcidin, a peptide produced in the liver and immunocompetent cells, impairs the expression of ferroportin on iron-secreting cells, thus reducing iron bioavailability. The typical changes of iron metabolism and hepcidin synthesis in RA are induced by proinflammatory cytokines, primarily interleukin-6. Hence, the treatment of RA with cytokine antagonists has significant therapeutic implications on anemia in the context of inflammation and impaired iron metabolism.

  5. Severe Aplastic Anemia Associated With Eosinophilic Fasciitis

    PubMed Central

    de Masson, Adèle; de Latour, Régis Peffault; Benhamou, Ygal; Moluçon-Chabrot, Cécile; Bay, Jacques-Olivier; Laquerrière, Annie; Picquenot, Jean-Michel; Michonneau, David; Leguy-Seguin, Vanessa; Rybojad, Michel; Bonnotte, Bernard; Jardin, Fabrice; Lévesque, Hervé; Bagot, Martine; Socié, Gérard

    2013-01-01

    Abstract Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia. In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 18–71 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1). PMID:23429351

  6. Anemias excluding cobalamin and folate deficiencies.

    PubMed

    Dublis, Stephanie; Shah, Shefali; Nand, Sucha; Anderes, Elise

    2014-01-01

    Anemias are one of the commonest maladies affecting humans. They result from either a failure of production by the bone marrow (hypoproliferative), or from premature destruction or loss (hyperproliferative) of red cells. Hypoproliferative anemias typically result from deficiencies of essential nutrients, stem cell abnormalities or deficiency, and infiltrative processes of the bone marrow. In the hyperproliferative forms, the bone marrow function is normal and anemia results from bleeding or shortened erythrocyte lifespan due to hemoglobinopathies, red cell enzyme disorders, membrane defects, or external factors such as antibodies, trauma, or heat injury. The etiology of anemia is frequently obvious, but when obscure, a systematic diagnostic approach frequently yields the answer. It is important to realize that anemias are usually a consequence of another disease process, which must be identified. Without correction of the underlying disease process, the treatment is likely to fail.

  7. Linkage analysis of autopsy-confirmed familial Alzheimer disease supports an Alzheimer disease locus in 8q24.

    PubMed

    Sillén, Anna; Brohede, Jesper; Forsell, Charlotte; Lilius, Lena; Andrade, Jorge; Odeberg, Jacob; Kimura, Toru; Winblad, Bengt; Graff, Caroline

    2011-01-01

    We have previously reported the results of an extended genome-wide scan of Swedish Alzheimer disease (AD)-affected families; in this paper, we analyzed a subset of these families with autopsy-confirmed AD. We report the fine-mapping, using both microsatellite markers and single-nucleotide polymorphisms (SNPs), in the observed maximum logarithm of the odds (LOD)-2 unit (LOD(max)-2) region under the identified linkage peak, linkage analysis of the fine-mapping data with additionally analyzed pedigrees, and association analysis of SNPs selected from candidate genes in the linked interval. The subset was made on the criterion of at least one autopsy-confirmed AD case per family, resulting in 24 families. Linkage analysis of a family subset having at least one autopsy-confirmed AD case showed a significant nonparametric single-point LOD score of 4.4 in 8q24. Fine-mapping under the linkage peak with 10 microsatellite markers yielded an increase in the multipoint (mpt) LOD score from 2.1 to 3.0. SNP genotyping was performed on 21 selected candidate transcripts of the LOD(max)-2 region. Both family-based association and linkage analysis were performed on extended material from 30 families, resulting in a suggestive linkage at peak marker rs6577853 (mpt LOD score = 2.4). The 8q24 region has been implicated to be involved in AD etiology. Copyright © 2011 S. Karger AG, Basel.

  8. A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease.

    PubMed

    Farashi, Samaneh; Faramarzi Garous, Negin; Zeinali, Fatemeh; Vakili, Shadi; Ashki, Mehri; Imanian, Hashem; Najmabadi, Hossein; Azarkeivan, Azita; Tamaddoni, Ahmad

    2015-01-01

    α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects in the α-globin gene cluster can result in α-thal that may develop into a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Loss of one functional α gene, indicated as heterozygous α(+)-thal, shows minor hematological abnormalities. Homozygosity for α(+)- or heterozygosity for α(0)-thal have more severe hematological abnormalities due to a markedly reduced α chain output. At the molecular level, the absence of three α-globin genes resulting from the compound heterozygous state for α(0)- and α(+)-thal, lead to Hb H disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino acids and 3 bp of intronic sequence at the exon-intron boundary, in both the α-globin genes, detected by direct DNA sequencing. This duplication was identified in three patients originating from two different Iranian ethnic groups and one Arab during more than 12 years. The clinical presentation of these individuals varies widely from a mild asymptomatic anemia (heterozygote in α1-globin gene) to a severely anemic state, diagnosed as an Hb H individual requiring blood transfusion (duplication on the α2-globin gene in combination with the - -(MED) double α-globin gene deletion). The third individual, who was homozygous for this nt duplication on the α1-globin gene, showed severe hypochromic microcytic anemia and splenomegaly. In the last decade, numerous α-globin mutations have demonstrated the necessity of prenatal diagnosis (PND) for α-thal, and this study has contributed another mutation as important enough that needs to be considered.

  9. Safety and Efficacy of PDpoetin for Management of Anemia in Patients with end Stage Renal Disease on Maintenance Hemodialysis: Results from a Phase IV Clinical Trial.

    PubMed

    Javidan, Abbas Norouzi; Shahbazian, Heshmatollah; Emami, Amirhossein; Yekaninejad, Mir Saeed; Emami-Razavi, Hassan; Farhadkhani, Masoumeh; Ahmadzadeh, Ahmad; Gorjipour, Fazel

    2014-08-26

    Recombinant human erythropoietin (rHuEPO) is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2) years. 48.7% of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43) g/dL at beginning of the study and reached 10.96 (±2.23) g/dL after 4 months and showed significant increase overall (P<0.001). PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL). Anemia were successfully corrected in 49% of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis.

  10. Skewed X-chromosome inactivation and XIST locus methylation levels do not contribute to the lower prevalence of Parkinson's disease in females.

    PubMed

    Sharma, Amit; Kaut, Oliver; Pavlova, Anna; Fröhlich, Holger; Ahmad, Ashar; Schmitt, Ina; El-Maarri, Osman; Oldenburg, Johannes; Wüllner, Ullrich

    2017-09-01

    Parkinson's disease (PD) is a degenerative disorder of the nervous system and the cause of the majority of sporadic cases is unknown. Females are relatively protected from PD as compared with males and linkage studies suggested a PD susceptibility locus on the X chromosome. To determine a putative association of skewed X-chromosome inactivation (XCI) and PD, we examined XCI patterns using a human androgen receptor gene-based assay (HUMARA) and did not identify any association of skewed or random X inactivation with clinical heterogeneity among female PD patients. In addition, we sought to determine methylation-specific changes at the X-inactive specific transcript (XIST) locus, which is known to be responsible for initiating X inactivation. We observed a trend towards hypomethylation in the gene body region of the XIST locus in PD females which did not reach significance. Furthermore, we extended our analysis of DNA methylation across the entire X-chromosome which revealed no methylation-specific differences between PD females and healthy controls. Thus, we propose that skewed XCI and methylation levels on the entire X chromosome did not reveal changes which could account for the decreased PD susceptibility in females or suitable to use as a biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Intravenous Versus Oral Iron for the Treatment of Anemia in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Bonovas, Stefanos; Fiorino, Gionata; Allocca, Mariangela; Lytras, Theodore; Tsantes, Argirios; Peyrin-Biroulet, Laurent; Danese, Silvio

    2016-01-01

    Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD). Our aim was to evaluate the comparative efficacy and harm of intravenous (IV) versus oral iron supplementation for correcting anemia in adult IBD patients.We conducted a systematic review and meta-analysis to integrate evidence from randomized controlled trials having enrolled adults with IBD, and comparing IV versus oral iron (head-to-head) for correcting iron-deficiency anemia. Medline, Embase, Scopus, and the Web of Science database were searched through July 2015. The Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the ClinicalTrials.gov, and international conference proceedings were also investigated. Two reviewers independently abstracted study data and outcomes, and rated each trial's risk-of-bias. Pooled odds ratio (OR) estimates with their 95% CIs were calculated using fixed- and random-effects models.Five eligible studies, including 694 IBD patients, were identified. In meta-analysis, IV iron demonstrated a higher efficacy in achieving a hemoglobin rise of ≥2.0 g/dL as compared to oral iron (OR: 1.57, 95% CI: 1.13, 2.18). Treatment discontinuation rates, due to adverse events or intolerance, were lower in the IV iron groups (OR: 0.27, 95% CI: 0.13, 0.59). Similarly, the occurrence of gastrointestinal adverse events was consistently lower in the IV iron groups. On the contrary, serious adverse events (SAEs) were more frequently reported among patients receiving IV iron preparations (OR: 4.57, 95% CI: 1.11, 18.8); however, the majority of the reported SAEs were judged as unrelated or unlikely to be related to the study medication. We found no evidence of publication bias, or between-study heterogeneity, across all analyses. Risk of bias was high across primary studies, because patients and personnel were not blinded to the intervention.IV iron appears to be more effective and better tolerated than oral

  12. Acquired aplastic anemia in children.

    PubMed

    Hartung, Helge D; Olson, Timothy S; Bessler, Monica

    2013-12-01

    This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.

  13. Cooley's Anemia: A Psychosocial Directory.

    ERIC Educational Resources Information Center

    National Center for Education in Maternal and Child Health, Washington, DC.

    The directory is intended to aid patients and their families who are coping with the genetic disorder of Cooley's anemia. A brief review of the disease covers background, genetics, symptoms, effect on the patient, treatment, and current research. The next section looks at psychosocial needs at various times (time of diagnosis, infancy and toddler…

  14. Development of mixed-type autoimmune hemolytic anemia and Evans' syndrome following chicken pox infection in a case of low-titer cold agglutinin disease.

    PubMed

    Tanaka, Yumi; Masuya, Masahiro; Katayama, Naoyuki; Miyata, Eri; Sugimoto, Yuka; Shibasaki, Tetsunori; Yamamura, Kentaro; Ohishi, Kohshi; Minami, Nobuyuki; Shiku, Hiroshi; Nobori, Tsutomu

    2006-10-01

    We describe a patient with low-titer cold agglutinin disease (CAD) who developed mixed-type autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenia following chicken pox infection. At least 1 year before admission to hospital, the patient had mild hemolytic anemia associated with low-titer cold agglutinins. A severe hemolytic crisis and thrombocytopenia (Evans' syndrome) occurred several days after infection with chicken pox, and the patient was referred to our hospital. Serological findings revealed the presence of both cold agglutinins and warm-reactive autoantibodies against erythrocytes, and the diagnosis was mixed-type AIHA. Following steroid therapy, the hemoglobin (Hb) level and platelet count improved. The patient was closely followed over a 10-year period with recurrent documented hemolysis after viral or bacterial infections. Warm-reactive autoantibodies have not been detected in the last 2 years, and only the immunoglobulin M anti-I cold agglutinins with a low titer and wide thermal amplitude have remained unchanged. Therefore, the patient has received at least 10 mg prednisolone daily to maintain a Hb level of 10 g/dL. To the best of our knowledge, no adult case of low-titer CAD that has evolved into mixed-type AIHA and Evans' syndrome after chicken pox infection has been previously reported in the literature.

  15. Optimal management of pernicious anemia

    PubMed Central

    Andres, Emmanuel; Serraj, Khalid

    2012-01-01

    Pernicious anemia (also known as Biermer’s disease) is an autoimmune atrophic gastritis, predominantly of the fundus, and is responsible for a deficiency in vitamin B12 (cobalamin) due to its malabsorption. Its prevalence is 0.1% in the general population and 1.9% in subjects over the age of 60 years. Pernicious anemia represents 20%–50% of the causes of vitamin B12 deficiency in adults. Given its polymorphism and broad spectrum of clinical manifestations, pernicious anemia is a great pretender. Its diagnosis must therefore be evoked and considered in the presence of neurological and hematological manifestations of undetermined origin. Biologically, it is characterized by the presence of anti-intrinsic factor antibodies. Treatment is based on the administration of parenteral vitamin B12, although other routes of administration (eg, oral) are currently under study. In the present update, these various aspects are discussed with special emphasis on data of interest to the clinician. PMID:23028239

  16. Cost of managing anemia in end-stage renal disease: the experience of five French dialysis centers.

    PubMed

    Rottembourg, Jacques; Tilleul, Patrick; Deray, Gilbert; Lafuma, Antoine; Zakin, Lorraine; Mahi, Lamine; Wernli, Jorge

    2015-05-01

    The aim of this retrospective study was to evaluate the direct cost of anemia treatment in hemodialysis patients and to evidence factors predictive of 1-year cost. Retrospective study which included hemodialyzed patients during year 2009 in five centers. Patients were evaluable if they had at least one hemoglobin (Hb) assay per month and were monitored for at least 4 months. Patients were classified in different "annual Hb category" according to their monthly mean Hb [Hb categories: Ideal (10 ≤ Hb ≤ 12 g/dL); High (Hb > 12 g/dL) and Low (Hb < 10 g/dL) if >75% of time in respective category, otherwise classified in the Fluctuating category]. We analyzed 636 patients (male, 59.4%) with a mean age of 67 years who underwent 144 hemodialysis sessions (median number per patient) in 2009. The cost of anemia treatment was largely driven by erythropoiesis-stimulating agents (ESA) (68% of total cost for Low Hb category and approximately 90% for the other Hb categories). Adjusted predictive factors for 1-year direct cost of anemia treatment (p < 0.0001) were dialysis center (2,518-5,617), death (6,091 vs. 4,911), age (4,911 for ≤55 years and 5,378 for 65-75 years), female gender (4,911 vs. 4,398 for male), Low Hb category (13,005 vs. 5,034 for Ideal, 4,911 for Fluctuating and 2,418 for High), serum ferritin level (5,102 for 200-500 μg/mL and 4,646 for ≥500 μg/mL) and duration of dialysis (4,911 if ≤2 years and 2,952 if 4-6 years). Retrospective study, and low number of patients in the Low Hb category. The main factors that were predictive of 1-year cost of anemia treatment in hemodialysis patients were centers, patients in the Low Hb category, and dialysis duration of less than 2 years.

  17. Investigation of nonpoikilocytic normochromic normocytic anemia.

    PubMed

    Ward, P C

    1979-03-01

    When the mean corpuscular volume is normal in an anemic patient, examination of a blood smear becomes of paramount importance. When the RBCs are normochronic, normocytic, and nonpoikilocytic, the reticulocyte count determines the line of investigation. When the count is increased, either hemorrhage or hemolysis is present. When the count is not increased (ie, normal or low), the differential diagnosis includes anemias due to iron deficiency, chronic disease, renal disease, hemodilution, marrow infiltration, and marrow failure (aplastic anemia). Some morphologic clues to cause other than those pertaining to RBC morphology are discussed and illustrated. A working approach to the investigation of nonpoikilocytic normochromic normocytic anemia is suggested.

  18. The GNAS complex locus and human diseases associated with loss-of-function mutations or epimutations within this imprinted gene

    PubMed Central

    Turan, Serap; Bastepe, Murat

    2013-01-01

    GNAS is a complex imprinted locus leading to several different gene products that show exclusive monoallelic expression. GNAS also encodes the alpha-subunit of the stimulatory G protein (Gsα), a ubiquitously expressed signaling protein that is essential for the actions of many hormones and other endogenous molecules. Gsα is expressed biallelically in most tissues but its expression is silenced from the paternal allele in a small number of tissues. The tissue-specific paternal silencing of Gsα results in different parent-of-origin specific phenotypes in patients who carry inactivating GNAS mutations. In this paper, we review the GNAS complex locus and discuss how disruption of Gsα expression and the expression of other GNAS products shape the phenotypes of human disorders caused by mutations in this gene. PMID:24107509

  19. Clinical and economic outcomes in Medicare beneficiaries with stage 3 or stage 4 chronic kidney disease and anemia: the role of intravenous iron therapy.

    PubMed

    Knight, Tyler G; Ryan, Kellie; Schaefer, Caroline P; D'Sylva, Lynell; Durden, Emily D

    2010-10-01

    Anemia in patients with chronic kidney disease (CKD) is associated with increased morbidity and mortality, decreased quality of life, and substantial health care costs. Iron therapy is recommended, usually in combination with an erythropoiesis-stimulating agent (ESA), in many CKD patients with anemia and low iron levels to raise hemoglobin levels to a range of 10 to 12 grams per deciliter; iron deficiency is defined by a ferritin score less than 100 micrograms (mcg) per liter and transferrin saturation (TSAT) less than 20%. To examine the use of intravenous (IV) iron and its associated economic and clinical outcomes in Medicare beneficiaries with stage 3 or stage 4 CKD and anemia. This was a retrospective cohort analysis using 2006 and 2007 Medicare 5% Standard Analytic Files (SAF). Use of therapy with IV iron and/or ESAs was identified among patients diagnosed with CKD and anemia. The study index quarter was the first quarter in 2006 during which the patient had primary or secondary diagnoses of both CKD and anemia. Based on the receipt of IV iron or ESA treatment in the index quarter, patients were classified into 1 of 4 treatment groups: IV iron and ESA; IV iron without ESA; ESA without IV iron; neither IV iron nor ESA. Therapy with oral iron was not measurable with this database. Clinical and economic outcomes, including the progression to advanced CKD stages, development of anemia, mortality, hospitalization, and net Medicare reimbursement (i.e., not including patient or supplemental plan contribution) for all-cause health care services, were examined for 1 year following the index quarter. Between-group differences were tested using Pearson chi-square for categorical variables and the Kruskal-Wallis nonparametric test for reimbursement. Multivariate logistic regression models were estimated to assess the associations of mortality, inpatient hospitalization, skilled nursing facility (SNF) admission, and hospice care with treatment regimen, controlling for

  20. Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2.

    PubMed Central

    San Millán, J L; Viribay, M; Peral, B; Martínez, I; Weissenbach, J; Moreno, F

    1995-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In approximately 86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of approximately 1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2. PMID:7825585

  1. Identification of Genetic Loci Affecting the Severity of Symptoms of Hirschsprung Disease in Rats Carrying Ednrbsl Mutations by Quantitative Trait Locus Analysis

    PubMed Central

    Torigoe, Daisuke; Lei, Chuzhao; Lan, Xianyong; Chen, Hong; Sasaki, Nobuya; Wang, Jinxi; Agui, Takashi

    2015-01-01

    Hirschsprung’s disease (HSCR) is a congenital disease in neonates characterized by the absence of the enteric ganglia in a variable length of the distal colon. This disease results from multiple genetic interactions that modulate the ability of enteric neural crest cells to populate developing gut. We previously reported that three rat strains with different backgrounds (susceptible AGH-Ednrbsl/sl, resistant F344-Ednrbsl/sl, and LEH-Ednrbsl/sl) but the same null mutation of Ednrb show varying severity degrees of aganglionosis. This finding suggests that strain-specific genetic factors affect the severity of HSCR. Consistent with this finding, a quantitative trait locus (QTL) for the severity of HSCR on chromosome (Chr) 2 was identified using an F2 intercross between AGH and F344 strains. In the present study, we performed QTL analysis using an F2 intercross between the susceptible AGH and resistant LEH strains to identify the modifier/resistant loci for HSCR in Ednrb-deficient rats. A significant locus affecting the severity of HSCR was also detected within the Chr 2 region. These findings strongly suggest that a modifier gene of aganglionosis exists on Chr 2. In addition, two potentially causative SNPs (or mutations) were detected upstream of a known HSCR susceptibility gene, Gdnf. These SNPs were possibly responsible for the varied length of gut affected by aganglionosis. PMID:25790447

  2. Marked phenotypic heterogeneity associated with expansion of a CAG repeat sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus

    SciTech Connect

    Cancel, G.; Abbas, N.; Stevanin, G.

    1995-10-01

    The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with those with Machado-Joseph disease (MJD), the gene of which maps to the same region. We show here that the disease gene segregating in each of three French ADCA type I kindreds and in a French family with neuropathological findings suggesting the ataxochoreic form of dentatorubropallidoluysian atrophy carries an expanded CAG repeat sequence located at the same locus as that for MJD. Analysis of the mutation in these families shows a strong negative correlation between size of the expanded CAG repeat and age at onset of clinical disease. Instability of the expanded triplet repeat was not found to be affected by sex of the parent transmitting the mutation. Evidence was found for somatic and gonadal mosaicism for alleles carrying expanded trinucleotide repeats. 36 refs., 5 figs., 2 tabs.

  3. Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2

    SciTech Connect

    San Millan, J.L.; Viribay, M.; Peral, B.; Moreno, F.; Martinez, I.; Weissenbach, J.

    1995-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In {approximately}86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of {approximately}1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2. 25 refs., 4 figs., 1 tab.

  4. The Anemias of Athletes.

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1986-01-01

    Diagnosing anemia in athletes is complicated because athletes normally have a pseudoanemia that needs no treatment. Athletes, however, can develop anemia from iron deficiency or footstrike hemolysis, which require diagnosis and treatment. (Author/MT)

  5. [Common anemias in neonatology].

    PubMed

    Humbert, J; Wacker, P

    1999-01-28

    We describe the four most common groups of neonatal anemia and their treatments, with particular emphasis on erythropoietin therapy. The hemolytic anemias include the ABO incompatibility (much more frequent, nowadays, than the Rh incompatibility, which has nearly disappeared following the use of anti-D immunoglobulin in postpartum Rh-negative mothers), hereditary spherocytosis and G-6-PD deficiency. Among hypoplastic anemias, that caused by Parvovirus B19 predominates, by far, over Diamond-Blackfan anemia, alpha-thalassemia and the rare sideroblastic anemias. "Hemorrhagic" anemias occur during twin-to-twin transfusions, or during feto-maternal transfusions. Finally, the multifactorial anemia of prematurity develops principally as a result of the rapid expansion of the blood volume in this group of patients. Erythropoietin therapy, often at doses much higher than those used in the adult, should be seriously considered in most cases of non-hypoplastic neonatal anemias, to minimise maximally the use of transfusions.

  6. The Anemias of Athletes.

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1986-01-01

    Diagnosing anemia in athletes is complicated because athletes normally have a pseudoanemia that needs no treatment. Athletes, however, can develop anemia from iron deficiency or footstrike hemolysis, which require diagnosis and treatment. (Author/MT)

  7. Anemia - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Anemia URL of this page: https://medlineplus.gov/languages/anemia.html Other topics A-Z Expand Section ...

  8. Erythropoietic stress and anemia in diabetes mellitus.

    PubMed

    Singh, Dhruv K; Winocour, Peter; Farrington, Ken

    2009-04-01

    Anemia is one of the world's most common preventable conditions, yet it is often overlooked, especially in people with diabetes mellitus. Diabetes-related chronic hyperglycemia can lead to a hypoxic environment in the renal interstitium, which results in impaired production of erythropoietin by the peritubular fibroblasts and subsequent anemia. Anemia in patients with diabetes mellitus might contribute to the pathogenesis and progression of cardiovascular disease and aggravate diabetic nephropathy and retinopathy. Anemia occurs earlier in patients with diabetic renal disease than in nondiabetic individuals with chronic kidney disease. Although erythropoietin has been used to treat renal anemia for nearly two decades, debate persists over the optimal target hemoglobin level. Most guidelines recommend that hemoglobin levels be maintained between 105g/l and 125g/l. The suggested role of anemia correction--to prevent the progression of left ventricular hypertrophy in patients with diabetes mellitus--is yet to be established. However, an emphasis on regular screening for anemia, alongside that for other diabetes-related complications, might help to delay the progression of vascular complications in these patients.

  9. Genetic diagnosis for congenital hemolytic anemia.

    PubMed

    Ohga, Shouichi

    Congenital hemolytic anemia is a group of monogenic diseases presenting with anemia due to increased destruction of circulating erythrocytes. The etiology of inherited anemia accounts for germline mutations of the responsible genes coding for the structural components of erythrocytes and extra-erythrocytes. The erythrocyte abnormalities are classified into three major disorders of red cell membrane defects, hemoglobinopathies, and red cell enzymopathies. The extra-erythrocyte abnormalities, typified by consumption coagulopathy and intravascular hemolysis, include Upshaw-Schulman syndrome and atypical hemolytic uremic syndrome. The clinical manifestations of congenital hemolytic anemia are anemia, jaundice, cholelithiasis and splenomegaly, while the onset mode and severity are both variable. Genetic overlapping of red cell membrane protein disorders, and distinct frequency and mutation spectra differing among races make it difficult to understand this disease entity. On the other hand, genetic modifiers for the phenotype of β-globin diseases provide useful information for selecting the optimal treatment and for long-term management. Recently, next generation sequencing techniques have enabled us to determine the novel causative genes in patients with undiagnosed hemolytic anemias. We herein review the concept and strategy for genetic diagnosis of inherited hemolytic anemias.

  10. The Evidence-Based Evaluation of Iron Deficiency Anemia.

    PubMed

    Hempel, Eliana V; Bollard, Edward R

    2016-09-01

    Anemia is a prevalent disease with multiple possible etiologies and resultant complications. Iron deficiency anemia is a common cause of anemia and is typically due to insufficient intake, poor absorption, or overt or occult blood loss. Distinguishing iron deficiency from other causes of anemia is integral to initiating the appropriate treatment. In addition, identifying the underlying cause of iron deficiency is also necessary to help guide management of these patients. We review the key components to an evidence-based, cost-conscious evaluation of suspected iron deficiency anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Myeloma and pernicious anemia.

    PubMed

    Perillie, P E

    1978-01-01

    Four cases of pernicious anemia developing in association with multiple myeloma are described. The description now of 14 cases demonstrating the association of these two disorders suggest a causative relationship. These observations, in addition to the previously well-documented increased coincidence of pernicious anemia and benign monoclonal gammopathy and pernicious anemia and hypoglobulinemia, suggest that screening for vitamine B12 deficiency in patients with gammopathies and for protein abnormalities in patients with pernicious anemia is indicated.

  12. Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

    PubMed Central

    Aaron, Grant J; Huang, Jin; Varadhan, Ravi; Temple, Victor; Rayco-Solon, Pura; Macdonald, Barbara

    2017-01-01

    Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts. Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6–59 mo) by country and infection-burden category. Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group. Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high–infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high–infection categories, respectively. Conclusions: Although causal inference is limited by

  13. Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: A parallel, randomized, double blind study

    PubMed Central

    Pérez-Oliva, Jorge F; Casanova-González, Martha; García-García, Idrian; Porrero-Martín, Pedro J; Valenzuela-Silva, Carmen M; Hernández-Montero, Tairí; Lagarde-Ampudia, Marcia; Casanova-Kutsareva, Yuri; Ávila-Albuerne, Yisel; Vargas-Batista, Alicia; Bobillo-López, Hailen; Herrera-Valdés, Raúl; López-Saura, Pedro A

    2005-01-01

    Background Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis. Methods A parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A), a newly developed product and Eprex (CILAG AG, Switzerland, formulation B), as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA) during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours. Results Both groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively). The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8 – 1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their intensity. The more

  14. Anemia (For Teens)

    MedlinePlus

    ... don't get enough iron in their diets. Iron Deficiency Anemia Iron deficiency anemia is the most common type of anemia ... when a person's diet is lacking in iron. Iron deficiency — when the body's stores of iron are reduced — ...

  15. Thiamine responsive megaloblastic anemia.

    PubMed

    Mathews, Lulu; Narayanadas, K; Sunil, G

    2009-02-01

    This report describes a female child with thiamine responsive megaloblastic anemia syndrome (Rogers syndrome), presenting with anemia and diabetes mellitus responding to thiamine. She also had retinitis pigmentosa. The anemia improved and blood sugar was controlled with daily oral thiamine. Previously unreported olfactory abnormalities, as described in Wolfram syndrome, were also present in our patient.

  16. Anemia: progress in molecular mechanisms and therapies.

    PubMed

    Sankaran, Vijay G; Weiss, Mitchell J

    2015-03-01

    Anemia is a major source of morbidity and mortality worldwide. Here we review recent insights into how red blood cells (RBCs) are produced, the pathogenic mechanisms underlying various forms of anemia, and novel therapies derived from these findings. It is likely that these new insights, mainly arising from basic scientific studies, will contribute immensely to both the understanding of frequently debilitating forms of anemia and the ability to treat affected patients. Major worldwide diseases that are likely to benefit from new advances include the hemoglobinopathies (β-thalassemia and sickle cell disease); rare genetic disorders of RBC production; and anemias associated with chronic kidney disease, inflammation, and cancer. Promising new approaches to treatment include drugs that target recently defined pathways in RBC production, iron metabolism, and fetal globin-family gene expression, as well as gene therapies that use improved viral vectors and newly developed genome editing technologies.

  17. Addison, pernicious anemia and adrenal insufficiency

    PubMed Central

    Graner, John L.

    1985-01-01

    In 1849 Thomas Addison described the clinical entity now known as pernicious anemia. In 1855 he reported several cases of adrenal insufficiency, or Addison's disease. Considering the importance of these works, there remains a great deal of confusion about them. Contrary to what many historians have written, a review of Addison's original publications demonstrates a firm appreciation of the distinction between pernicious anemia and adrenal insufficiency, based particularly on the discoloration of the skin in these conditions. Three major sources of possible confusion for historians who are attempting to understand Addison's views include Addison's early attempts to link pernicious anemia with disease of the supra-renal capsules, Addison's redefinition of pernicious anemia in his monograph on adrenal disease, and several confusing statements made by Wilks and Daldy in the first reprint of Addison's monograph. ImagesFig. 1 PMID:3902186

  18. A case of asymptomatic pancytopenia with clinical features of hemolysis as a presentation of pernicious anemia

    PubMed Central

    Kollipara, Venkateswara K.; Brine, Patrick L.; Gemmel, David; Ingnam, Sisham

    2016-01-01

    Pernicious anemia is an autoimmune disease with a variety of clinical presentations. We describe a case of pernicious anemia presenting with pancytopenia with hemolytic features. Further workup revealed very low vitamin B12 levels and elevated methylmalonic acid. It is important for a general internist to identify pernicious anemia as one of the cause of pancytopenia and hemolytic anemia to avoid extensive workup. Pernicious anemia can present strictly with hematological abnormalities without neurological problems or vice versa as in our case. PMID:27609735

  19. A Novel Antisense CAG Repeat Transcript at JPH3 Locus Mediating Expanded Polyglutamine Protein Toxicity in Huntington’s Disease-Like 2 (HDL2) Mice

    PubMed Central

    Wilburn, Brian; Rudnicki, Dobrila D.; Zhao, Jing; Weitz, Tara Murphy; Cheng, Yin; Gu, Xiaofeng; Greiner, Erin; Park, Chang Sin; Wang, Nan; Sopher, Bryce L.; La Spada, Albert R.; Osmand, Alex; Margolis, Russell L.; Sun, Yi E.; Yang, X. William

    2011-01-01

    SUMMARY Huntington’s disease like-2 (HDL2) is a phenocopy of Huntington’s disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology and ubiquitin-positive nuclear inclusions (NIs). Molecular analyses reveal a novel promoter at the transgene locus driving the expression of a CAG repeat transcript (HDL2-CAG) from the strand antisense to JPH3, which encodes an expanded polyglutamine (polyQ) protein. Importantly, BAC-HDL2 but not control BAC mice accumulate polyQ-containing NIs in a pattern strikingly similar to those in the patients. Furthermore, BAC mice with genetic silencing of the expanded CUG transcript still express HDL2-CAG transcript and manifest polyQ pathogenesis. Finally, studies of HDL2 mice and patients revealed CBP sequestration into NIs and evidence for interference of CBP-mediated transcriptional activation. These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2 PMID:21555070

  20. The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

    PubMed Central

    Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-01-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25–55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19–3.66) as well as the G allele (OR=1.49, 95% CI: 1.08–2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population. PMID:22946666

  1. The rs10757278 polymorphism of the 9p21.3 locus is associated with premature coronary artery disease in Polish patients.

    PubMed

    Niemiec, Pawel; Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-09-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25-55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19-3.66) as well as the G allele (OR=1.49, 95% CI: 1.08-2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.

  2. Management of Iron Deficiency Anemia

    PubMed Central

    Jimenez, Kristine; Kulnigg-Dabsch, Stefanie

    2015-01-01

    Anemia affects one-fourth of the world’s population, and iron deficiency is the predominant cause. Anemia is associated with chronic fatigue, impaired cognitive function, and diminished well-being. Patients with iron deficiency anemia of unknown etiology are frequently referred to a gastroenterologist because in the majority of cases the condition has a gastrointestinal origin. Proper management improves quality of life, alleviates the symptoms of iron deficiency, and reduces the need for blood transfusions. Treatment options include oral and intravenous iron therapy; however, the efficacy of oral iron is limited in certain gastrointestinal conditions, such as inflammatory bowel disease, celiac disease, and autoimmune gastritis. This article provides a critical summary of the diagnosis and treatment of iron deficiency anemia. In addition, it includes a management algorithm that can help the clinician determine which patients are in need of further gastrointestinal evaluation. This facilitates the identification and treatment of the underlying condition and avoids the unnecessary use of invasive methods and their associated risks. PMID:27099596

  3. Erythropoietin Levels in Elderly Patients with Anemia of Unknown Etiology

    PubMed Central

    Sriram, Swetha; Martin, Alison; Xenocostas, Anargyros; Lazo-Langner, Alejandro

    2016-01-01

    Background In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of “anemia of unknown etiology” and whether this trend persists after accounting for confounders. Methods This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient’s anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index. Results A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities. Conclusions We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology. PMID:27310832

  4. Biomarkers for the differentiation of anemia and their clinical usefulness.

    PubMed

    Northrop-Clewes, Christine A; Thurnham, David I

    2013-01-01

    The World Health Organization defines anemia as the point at which the amount of hemoglobin in the circulation falls below World Health Organization cutoffs for specific age and sex groups. Anemia is a worldwide problem of complex etiology and is associated with many factors. The purpose of this review was to describe the biomarkers used to identify the nature of anemia in patients and in the community. The important biomarkers are the automated red cell counts, tests for nutritional deficiencies, hemoglobinopathies, and inflammation. Diseases are important potential initiators of anemia, but biomarkers of specific diseases are not included in this review, only the underlying feature common to all disease - namely, inflammation.

  5. Targeted gene therapy and cell reprogramming in Fanconi anemia

    PubMed Central

    Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

    2014-01-01

    Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. PMID:24859981

  6. Advancements in anemias related to chronic conditions.

    PubMed

    Guidi, Gian Cesare; Lechi Santonastaso, Clara

    2010-09-01

    Anemia of chronic disease (ACD), the most frequent anemia among hospitalized patients, occurs in chronic inflammatory disorders, such as chronic infections, cancer and autoimmune diseases. Different causes contribute to ACD including diversion of iron traffic, diminished erythropoiesis, blunted response to erythropoietin, erythrophagocytosis, hematologic malignancies and solid tumors. A particular case of ACD is represented by anemia of chronic kidney disease (CKD). ACD is characterized by hyposideremia and altered iron transport. Cytokines are implicated in the ACD by reducing erythropoiesis and increasing iron sequestration in the reticuloendothelial system. The regulation of iron absorption across the epithelium of the proximal small intestine is essential for maintaining body iron concentrations within a physiologically defined range. Hepcidin controls cellular iron efflux by binding to the iron export protein ferroportin, causing ferroportin to be phosphorylated and degraded in lysosomes. Finally, hepcidin inhibits iron release from the reticulo-endothelial system. Increased expression of hepcidin leads to decreased iron absorption and iron deficient anemia. Hepcidin, therefore, is a negative regulator of iron transport in plasma. Causes of anemia in patients with CKD are multifactorial, but the most well-known cause is inadequate erythropoietin production. In these patients, anemia increases the risk of either cardiovascular disease or renal failure.

  7. Role of Complement in Autoimmune Hemolytic Anemia.

    PubMed

    Berentsen, Sigbjørn

    2015-09-01

    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  8. Role of Complement in Autoimmune Hemolytic Anemia

    PubMed Central

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed. PMID:26696798

  9. Anemia of immobility: caused by adipocyte accumulation in bone marrow.

    PubMed

    Payne, Michael W C; Uhthoff, Hans K; Trudel, Guy

    2007-01-01

    Anemia of chronic disease has long been used to classify a non-regenerative, low-grade, chronic, normocytic, normochromic anemia that presents with no obvious etiology. Within this group, some patients have a chronic inflammatory condition that limits erythrocyte generation or access to iron stores. This specific type of anemia has been termed anemia of chronic inflammation. However, a substantial remainder of patients diagnosed with anemia of chronic disease present with no active inflammation. These include many clinical populations with reduced limb loading, such as spinal cord injured patients, astronauts, elderly people with limited mobility and experimental bed-rest subjects. In some populations with decreased mobility, accumulation of fat in the bone marrow has been demonstrated. We hypothesize that adipocyte accumulation in bone marrow both passively and actively impairs erythropoiesis and thus defines a new type of anemia called anemia of immobility. The non-specific umbrella term anemia of chronic disease thus becomes obsolete in favour of either the diagnosis of anemia of immobility or anemia of chronic inflammation according to the distinct mechanism involved.

  10. Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping.

    PubMed Central

    Neufeld, E J; Mandel, H; Raz, T; Szargel, R; Yandava, C N; Stagg, A; Fauré, S; Barrett, T; Buist, N; Cohen, N

    1997-01-01

    Thiamine-responsive megaloblastic anemia, also known as "TRMA" or "Rogers syndrome," is an early-onset autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine treatment. On the basis of a linkage analysis of affected families of Alaskan and of Italian origin, we found, using homozygosity mapping, that the TRMA-syndrome gene maps to a region on chromosome 1q23.2-23.3 (maximum LOD score of 3.7 for D1S1679). By use of additional consanguineous kindreds of Israeli-Arab origin, the putative disease-gene interval also has been confirmed and narrowed, suggesting genetic homogeneity. Linkage analysis generated the highest combined LOD-score value, 8.1 at a recombination fraction of 0, with marker D1S2799. Haplotype analysis and recombination events narrowed the TRMA locus to a 16-cM region between markers D1S194 and D1S2786. Several heterozygote parents had diabetes mellitus, deafness, or megaloblastic anemia, which raised the possibility that mutations at this locus predispose carriers in general to these manifestations. Characterization of the metabolic defect of TRMA may shed light on the role of thiamine deficiency in such common diseases. PMID:9399900

  11. Somatic variation plays a key role in the evolution of the Vf gene family residing in the Vf locus that confers resistance to apple scab disease.

    PubMed

    Xu, Mingliang; Korban, Schuyler S

    2004-07-01

    A cluster of four receptor-like genes has been previously identified in the Vf locus of the crabapple Malus floribunda clone 821 that confers resistance to five races of the fungal pathogen Venturia inaequalis, the casual agent of apple scab disease. Pairwise comparisons of the four Vf paralogs in both promoter and coding regions reveal their timeline evolutionary history. The four Vf paralogs have evolved from four ancient Vf members resulting from two sequential duplication events of a single Vf progenitor initially present in the Malus genome. The coding sequences of the four Vf paralogs are characterized with high numbers of unique polymorphic nucleotides, a number of short duplications/deletions, various deletions of complete LRR copy units, and a casual insert of a transposon-like element. Significant high ratios of nonsynonymous to synonymous substitutions, Ka/Ks, are observed in the putative ligand binding residues in the LRR domains. No sequence exchange between the four Vf paralogs is observed. Compared with promoter regions, only nucleotide substitutions are dramatically elevated in the coding regions. The results presented in this study strongly indicate that the Vf locus is under strong and steady horizontal selective pressures imposed by the fungal pathogen V. inaequalis, and divergent selection on somatic variations plays a key role in shaping the resistance specificity.

  12. Unexpected Anemia and Reticulocytopenia in an Adolescent With Sickle Cell Anemia Receiving Chronic Transfusion Therapy.

    PubMed

    Blauel, Emily R; Grossmann, Lily T; Vissa, Madhav; Miller, Scott T

    2015-10-01

    In a patient with sickle cell disease receiving chronic transfusion, exacerbation of anemia with reticulocytopenia must prompt consideration of a delayed hemolytic transfusion reaction with hyperhemolysis, as further transfusion may worsen this condition; definitive diagnosis is sometimes difficult. Anemia evolving during parvovirus B19-induced erythroid hypoplasia (transient aplastic crisis) should be attenuated in chronic transfusion patients due to superior survival of transfused over endogenous red blood cells. A 16-year-old with sickle cell disease receiving chronic transfusion of modified intensity (goal to maintain hemoglobin S<50%) who developed symptomatic anemia with reticulocytopenia was later shown to have had transient aplastic crisis.

  13. Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4C locus SH3TC2.

    PubMed

    Brewer, Megan Hwa; Ma, Ki Hwan; Beecham, Gary W; Gopinath, Chetna; Baas, Frank; Choi, Byung-Ok; Reilly, Mary M; Shy, Michael E; Züchner, Stephan; Svaren, John; Antonellis, Anthony

    2014-10-01

    Loss-of-function mutations in the Src homology 3 (SH3) domain and tetratricopeptide repeats 2 (SH3TC2) gene cause autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy. The SH3TC2 protein has been implicated in promyelination signaling through axonal neuregulin-1 and the ERBB2 Schwann cell receptor. However, little is known about the transcriptional regulation of the SH3TC2 gene. We performed computational and functional analyses that revealed two cis-acting regulatory elements at SH3TC2-one at the promoter and one ∼150 kb downstream of the transcription start site. Both elements direct reporter gene expression in Schwann cells and are responsive to the transcription factor SOX10, which is essential for peripheral nervous system myelination. The downstream enhancer harbors a single-nucleotide polymorphism (SNP) that causes an ∼80% reduction in enhancer activity. The SNP resides directly within a predicted binding site for the transcription factor cAMP response element binding protein (CREB), and we demonstrate that this regulatory element binds to CREB and is activated by CREB expression. Finally, forskolin induces Sh3tc2 expression in rat primary Schwann cells, indicating that SH3TC2 is a CREB target gene. These findings prompted us to determine if SNP genotypes at SH3TC2 are associated with differential phenotypes in the most common demyelinating peripheral neuropathy, CMT1A. Interestingly, this revealed several associations between SNP alleles and disease severity. In summary, our data indicate that SH3TC2 is regulated by the transcription factors CREB and SOX10, define a regulatory SNP at this disease-associated locus and reveal SH3TC2 as a candidate modifier locus of CMT disease phenotypes.

  14. Fanconi's Anemia Effect or Sickle Cell Anemia Effect: That is the Question.

    PubMed

    Unal, Sule; Chui, David H K; Gumruk, Fatma

    2015-01-01

    A 16-year-old boy who was diagnosed to have sickle cell anemia was referred to our center. The parental consanguinity, growth retardation and dysmorphic features prompted a search for possible Fanconi's Anemia (FA). The diepoxybutane (DEB) test was positive, confirming FA. The interaction of both diseases might account for his relatively mild phenotype in terms of both sickle cell anemia (or Hb S, HBB: c.20A > T) and FA. The high Hb F level that might be related to concomitant FA, may have caused a milder phenotype of sickle cell anemia, whereas nitric oxide (NO) depletion as a consequence of sickle cell anemia, may have caused a delay in the bone marrow failure of FA.

  15. [Do we successfully treat anemia and calcium-phosphate disorders in children with chronic kidney disease at the beginning of the twenty-first century?].

    PubMed

    Drożdż, Dorota; Kwinta, Przemko; Sztefko, Krystyna; Zachwieja, Katarzyna; Miklaszewska, Monika; Drożdż, Tomasz; Łatka, Monika; Pietrzyk, Jacek A

    2015-01-01

    In children with chronic kidney disease (CKD) anemia and calcium-phosphate disturbances are already present at early stages of the disease and require a comprehensive treatment. The aim of this study was to evaluate the efficacy of the treatment of biochemical disturbances, depending on the severity of CKD in children. The study included 71 children (44 boys, 27 girls) with CKD stage 1-5. Mean age was 11 ± 5 years, mean height: 135.7 ± 28 cm and mean eGFR 32 ml/min/1.73 m2. The serum hemoglobin, urea, creatinine, cystatin C, calcium, phosphorus and parathyroid hormone (PTH) levels were measured. eGFR was calculated according to Schwartz and Filler formulas, employing creatinine and cystatin C as markers. Patients were divided into groups depending on the stage of CKD [group 1: CKD stage 1+2 (GFR > 60), group 2: CKD stage 3 (GFR = 30-59) Group 3: CKD stage 4 (GFR = 15-29 ml/min/1.73 m2), group 4 - dialyzed children]. The concentration of he- moglobin depending on the stage of CKD (group 1 vs. group 2 vs. group 3 vs group 4) was 12.95 vs. 12.68 vs. 12.47 vs. 11.3 g/dI, respectively. The concentration of total and ionized calcium was significantly lower in children on dialysis compared to patients treated conservatively. With the progression of CKD the concentration of phosphorus (1.39 vs. 1.4 vs. 1.49 vs. 1.82 mmolI) and PTH (21.7 vs 48.6 vs 99.9 vs. 219 pg/ml) significantly increased. Treatment with erythropoietin was used in 48% of children, calcium carbonate in 55% and alphacalcidol in 56% of patients. Despite the use of regular treatment, with the progression of CKD a progression of anemia, increased serum phosphate and parathyroid hormone and a decrease in calcium levels in studied children was observed. The severity of metabolic disorders in dialyzed children indicates the need for administration of new and more effective drugs, to prevent early enough complications of CKD in the form of mineral bone disease and cardiovascular complications.

  16. Ferric Maltol Is Effective in Correcting Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease: Results from a Phase-3 Clinical Trial Program

    PubMed Central

    Ahmad, Tariq; Tulassay, Zsolt; Baumgart, Daniel C.; Bokemeyer, Bernd; Büning, Carsten; Howaldt, Stefanie; Stallmach, Andreas

    2014-01-01

    Background: Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease. Traditionally, oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation. This multicenter phase-3 study tested the efficacy and safety of ferric maltol, a complex of ferric (Fe3+) iron with maltol (3-hydroxy-2-methyl-4-pyrone), as a novel oral iron therapy for IDA. Methods: Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn's disease, mild-to-moderate IDA (9.5–12.0 g/dL and 9.5–13.0 g/dL in females and males, respectively), and documented failure on previous oral ferrous products received oral ferric maltol capsules (30 mg twice a day) or identical placebo for 12 weeks according to a randomized, double-blind, placebo-controlled study design. The primary efficacy endpoint was change in hemoglobin (Hb) from baseline to week 12. Safety and tolerability were assessed. Results: Of 329 patients screened, 128 received randomized therapy (64 ferric maltol-treated and 64 placebo-treated patients) and comprised the intent-to-treat efficacy analysis: 55 ferric maltol patients (86%) and 53 placebo patients (83%) completed the trial. Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4, 8, and 12: mean (SE) 1.04 (0.11) g/dL, 1.76 (0.15) g/dL, and 2.25 (0.19) g/dL, respectively (P < 0.0001 at all time-points; analysis of covariance). Hb was normalized in two-thirds of patients by week 12. The safety profile of ferric maltol was comparable with placebo, with no impact on inflammatory bowel disease severity. Conclusions: Ferric maltol provided rapid clinically meaningful improvements in Hb and showed a favorable safety profile, suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease. PMID:25545376

  17. Anemia, fatigue and aging.

    PubMed

    Balducci, L

    2010-12-01

    Aging is associated with increased incidence and prevalence of both cancer and anemia. Cancer and aging may conspire in making anemia more frequent and more severe. This article reviews the causes and the consequences of anemia in the older individual. The most common causes include chronic inflammation that is a typical manifestation of aging, iron deficiency that may be due to chronic hemorrhage, malabsorption and Helicobacter pylori infection, cobalamin deficiency from malabsorption and renal insufficiency. Other causes of anemia whose prevalence is not well established include myelodysplasia, copper deficiency, hypothyroidism, and sarcopenia. Anemia is associated with increased risk of mortality, functional dependence, dementia, falls, and chemotherapy-related toxicity. When correcting the anemia of older cancer patients one should remember that the erythropoietic stimulating agents (ESA) may stimulate cancer growth and cause thrombosis. These products may be safe when given exclusively to patients receiving chemotherapy and when the hemoglobin levels are maintained below 12 g/dL.

  18. Relationships between systemic vascular resistance, blood rheology and nitric oxide in children with sickle cell anemia or sickle cell-hemoglobin C disease.

    PubMed

    Lamarre, Yann; Hardy-Dessources, Marie-Dominique; Romana, Marc; Lalanne-Mistrih, Marie-Laure; Waltz, Xavier; Petras, Marie; Doumdo, Lydia; Blanchet-Deverly, Anne; Martino, Jean; Tressières, Benoît; Maillard, Frederic; Tarer, Vanessa; Etienne-Julan, Maryse; Connes, Philippe

    2014-01-01

    Vascular function has been found to be impaired in patients with sickle cell disease (SCD). The present study investigated the determinants of systemic vascular resistance in two main SCD syndromes in children: sickle cell anemia (SCA) and sickle cell-hemoglobin C disease (SCC). Nitric oxide metabolites (NOx), hematological, hemorheological, and hemodynamical parameters were investigated in 61 children with SCA and 49 children with SCC. While mean arterial pressure was not different between SCA and SCC children, systemic vascular resistance (SVR) was greater in SCC children. Although SVR and blood viscosity (ηb) were not correlated in SCC children, the increase of ηb (+18%) in SCC children compared to SCA children results in a greater mean SVR in this former group. SVR was positively correlated with ηb, hemoglobin (Hb) level and RBC deformability, and negatively with NOx level in SCA children. Multivariate linear regression model showed that both NOx and Hb levels were independently associated with SVR in SCA children. In SCC children, only NOx level was associated with SVR. In conclusion, vascular function of SCC children seems to better cope with higher ηb compared to SCA children. Since the occurrence of vaso-occlusive like complications are less frequent in SCC than in SCA children, this finding suggests a pathophysiological link between the vascular function alteration and these clinical manifestations. In addition, our results suggested that nitric oxide metabolism plays a key role in the regulation of SVR, both in SCA and SCC.

  19. Musculoskeletal manifestations of chronic anemias.

    PubMed

    Martinoli, Carlo; Bacigalupo, Lorenzo; Forni, Gian Luca; Balocco, Manuela; Garlaschi, Giacomo; Tagliafico, Alberto

    2011-07-01

    This article provides an overview of the current use of diagnostic imaging modalities in the evaluation of a heterogeneous group of disorders causing chronic anemias by impaired blood cell production (inherited bone marrow failure syndromes of childhood, aplastic anemia and myelodysplastic syndromes, β-thalassemia) or increased blood cell destruction (sickle cell disease). During the course of these disorders, various musculoskeletal abnormalities can be encountered, including marrow hyperplasia, reversion of yellow marrow to red marrow, growth disturbances, and, occasionally, extramedullary hematopoiesis. Diagnostic imaging may help the clinician to identify specific complications related to either the disease (e.g., bone infarction and acute osteomyelitis in sickle cell disease) or transfusion (e.g., iron overload due to increased hemolysis) and iron chelation (e.g., desferrioxamine-related dysplastic bone changes and deferiprone-related degenerative arthritis) treatments. In this field, magnetic resonance imaging plays a pivotal role because of its high tissue contrast that enables early assessment of bone marrow changes before they become apparent on plain films or computed tomography or metabolic changes occur on bone scintigraphy or positron emission tomography scan. Overall, familiarity with the range of radiological appearances in chronic anemias is important to diagnose complications and establish appropriate therapy. © Thieme Medical Publishers.

  20. The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1)

    SciTech Connect

    Tsugu, H.; Horowitz, R.; Gibson, N.

    1994-12-01

    Sera from approximately 30% of patients with systemic lupus erythematosus (SLE) contain high titers of autoantibodies that bind to the 52-kDa Ro/SSA protein. We previously detected polymorphisms in the 52-kDa Ro/SSA gene (SSA1) with restriction enzymes, one of which is strongly associated with the presence of SLE (P < 0.0005) in African Americans. A higher disease frequency and more severe forms of the disease are commonly noted among these female patients. To determine the location and nature of this polymorphism, we obtained two clones that span 8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six exons were identified, and their nucleotide sequences plus adjacent noncoding regions were determined. No differences were found between these exons and the coding region of one of the reported cDNAs. The disease-associated polymorphic site suggested by a restriction enzyme map and confirmed by DNA amplification and nucleotide sequencing was present upstream of exon 1. This polymorphism may be a genetic marker for a disease-related variation in the coding region for the protein or in the upstream regulatory region of this gene. Although this RFLP is present in Japanese, it is not associated with lupus in this race. 41 refs., 4 figs., 2 tabs.

  1. Inborn anemias in mice

    SciTech Connect

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes.

  2. Genetic defects at the UGT1 locus associated with Crigler-Najjar type I disease, including a prenatal diagnosis

    SciTech Connect

    Ciotti, M.; Obaray, R.; Owens, I.S.; Martin, M.G.

    1997-01-20

    Characterization of the UGT1 gene complex locus encoding both multiple bilirubin and phenol UDP-glucuronosyltransferases (transferases) has been critical in identifying mutations in the bilirubin isoforms. This study utilizes this information to identify the bases of deficient bilirubin UDP-glucuronosyltransferase activity encoded by the UGT1A gene for the major bilirubin isozyme, HUG-Br1, in 3 Crigler-Najjar type I individuals and the genotype of an at-risk unborn sibling of one patient. A homozygous and heterozygous two-base mutation (CCC to CGT) created the HUG-Br1P387R mutant of the major bilirubin transferase in 2 different Crigler-Najjar type I patients, B.G. and G.D., respectively. Both parents of B.G. and his unborn sibling, J.G., were determined to be carriers of the P387R mutation. G.D. also contains the CAA to TAA nonsense mutation (G1n357st). Y.A. has a homozygous CT deletion in codons 40/41. The HUG-Br1P387R mutant protein was totally inactive at the major pH optimum, but retained 26% normal activity at the minor pH optimum (7.6), which was 5.4% of the combined activities measured at the two pH values. 27 refs., 5 figs.

  3. Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

    PubMed Central

    López-Isac, Elena; Martín, Jose-Ezequiel; Assassi, Shervin; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre-Sancho, Juan J; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Ortiz, Ana M; González-Gay, Miguel A; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Witte, Torsten; Hunzelmann, Nicolas; Distler, Jörg HW; Riekemasten, Gabriella; van der Helm-van Mil, Annete H; de Vries-Bouwstra, Jeska; Magro-Checa, Cesar; Voskuyl, Alexandre E; Vonk, Madelon C; Molberg, Øyvind; Merriman, Tony; Hesselstrand, Roger; Nordin, Annika; Padyukov, Leonid; Herrick, Ariane; Eyre, Steve; Koeleman, Bobby PC; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy RDJ; Worthington, Jane; Mayes, Maureen D; Martín, Javier

    2017-01-01

    Objectives Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc-RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposing-direction allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 × 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 × 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci. PMID:27111665

  4. Anemia in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Barbieri, Jéssica; Fontela, Paula Caitano; Winkelmann, Eliane Roseli; Zimmermann, Carine Eloise Prestes; Sandri, Yana Picinin; Mallet, Emanelle Kerber Viera; Frizzo, Matias Nunes

    2015-01-01

    The objective of this study was to evaluate the prevalence of anemia in DM2 patients and its correlation with demographic and lifestyle and laboratory variables. This is a descriptive and analytical study of the type of case studies in the urban area of the Ijuí city, registered in programs of the Family Health Strategy, with a total sample of 146 patients with DM2. A semistructured questionnaire with sociodemographic and clinical variables and performed biochemical test was applied. Of the DM2 patients studied, 50 patients had anemia, and it was found that the body mass items and hypertension and hematological variables are significantly associated with anemia of chronic disease. So, the prevalence of anemia is high in patients with DM2. The set of observed changes characterizes the anemia of chronic disease, which affects quality of life of diabetic patients and is associated with disease progression, development, and comorbidities that contribute significantly to increasing the risk of cardiovascular diseases.

  5. Paraoxonase and arylesterase activities in children with iron deficiency anemia and vitamin B12 deficiency anemia.

    PubMed

    Koc, Ahmet; Cengiz, Murad; Ozdemir, Zeynep Canan; Celik, Hakim

    2012-05-01

    Paraoxonase-1 is an esterase enzyme and it has 3 types of activity, namely paraoxonase, arylesterase, and diazoxonase. It has been reported that paraoxonase-1 deficiency is related to increased susceptibility to development of atherosclerosis and cardiovascular disease. The aim of this study was to investigate serum paraoxonase and arylesterase activities in children with iron deficiency anemia and vitamin B(12) deficiency anemia. Thirty children with iron deficiency anemia, 30 children with vitamin B(12) deficiency anemia, and 40 healthy children aged 6 months to 6 years were enrolled in this study. Serum paraoxonase and arylesterase activities were measured with a spectrophotometer by using commercially available kits. Mean paraoxonase and arylesterase activities in vitamin B(12) deficiency anemia group (103 ± 73 and 102 ± 41 U/L, respectively) were significantly lower than mean activities of control group (188 ± 100 and 147 ± 34 U/L, respectively; P < .001 for both) and iron deficiency anemia group (165 ± 103 and 138 ± 39 U/L, respectively; P < .05, P < .001), whereas there were no significant differences between iron deficiency anemia and control groups (P > .05). Paraoxonase and arylesterase activities significantly increased after treatment with vitamin B(12) in vitamin B(12) deficiency anemia; however, there were no significant changes in the activities of these enzymes after iron treatment in iron deficiency anemia group. Important correlations were found between vitamin B(12) levels and both paraoxonase and arylesterase activities (r = .367, P < .001; r = .445, P < .001). Our results suggest that vitamin B(12) deficiency anemia causes important reductions in paraoxonase and arylesterase activities, and after vitamin B(12) therapy the activities of these enzymes returned to near-normal levels.

  6. Characteristics of anemia in subclinical and overt hypothyroid patients.

    PubMed

    Erdogan, Mehmet; Mehmet, Erdogan; Kösenli, Aybike; Aybike, Kosenli; Ganidagli, Sencer; Kulaksizoglu, Mustafa; Mustafa, Kulaksizoglu

    2012-01-01

    Thyroid hormones stimulate directly or indirectly growth of erythroid colonies through erythropoietin. Anemia is often the first sign of hypothyroidism. Hypothyroidism can cause a wide variety of anemic disorders. Numerous mechanisms are involved in the pathogenesis of these anemias that can be microcytic, macrocytic and normocytic. We designed this study to investigate the anemia frequency and if present, etiology of anemia in hypothyroid patients. 100 patients with overt hypothyroid, 100 patients with subclinical hypothyroid, and 200 healthy controls were enrolled in this study. Overt hypothyroidism diagnosis is done when elevated TSH and low levels of free T4 and/or free T3 have been observed. Subclinical hypothyroidism is defined as elevated serum TSH with normal free T(4) and free T(3) levels. Peripheral smears of the anemic patients were examined. Anemia prevalence was 43% in the overt hypothyroid group, 39% in the subclinical hypothyroid group, and 26% in the control group (p=0.0003 and p=0.021 respectively related to controls). Thus, the frequency of anemia in subclinical hypothyroidism is as high as that in overt hypothyroidism. There was no difference between the hypothyroid groups in terms of anemia. Vitamin B12, Fe, and folic acid were similar between these groups. According to our findings, anemia of chronic disease is the most common type of anemia in hypothyroid patients. Suspicion of hypothyroidism should be considered in anemias with uncertain etiology.

  7. Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease.

    PubMed

    Dharmadhikari, Avinash V; Szafranski, Przemyslaw; Kalinichenko, Vladimir V; Stankiewicz, Pawel

    2015-04-01

    The FOXF1 (Forkhead box F1) gene, located on chromosome 16q24.1 encodes a member of the FOX family of transcription factors characterized by a distinct forkhead DNA binding domain. FOXF1 plays an important role in epithelium-mesenchyme signaling, as a downstream target of Sonic hedgehog pathway. Heterozygous point mutations and genomic deletions involving FOXF1 have been reported in newborns with a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). In addition, genomic deletions upstream to FOXF1 identified in ACDMPV patients have revealed that FOXF1 expression is tightly regulated by distal tissue-specific enhancers. Interestingly, FOXF1 has been found to be incompletely paternally imprinted in human lungs; characterized genomic deletions arose de novo exclusively on maternal chromosome 16, with most of them being Alu-Alu mediated. Regulation of FOXF1 expression likely utilizes a combination of chromosomal looping, differential methylation of an upstream CpG island overlapping GLI transcription factor binding sites, and the function of lung-specific long non-coding RNAs (lncRNAs). FOXF1 knock-out mouse models demonstrated its critical role in mesoderm differentiation and in the development of pulmonary vasculature. Additionally, epigenetic inactivation of FOXF1 has been reported in breast and colorectal cancers, whereas overexpression of FOXF1 has been associated with a number of other human cancers, e.g. medulloblastoma and rhabdomyosarcoma. Constitutional duplications of FOXF1 have recently been reported in congenital intestinal malformations. Thus, understanding the genomic and epigenetic complexity at the FOXF1 locus will improve diagnosis, prognosis, and treatment of ACDMPV and other human disorders associated with FOXF1 alterations.

  8. Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease

    PubMed Central

    Dharmadhikari, Avinash V.; Szafranski, Przemyslaw; Kalinichenko, Vladimir V.; Stankiewicz, Pawel

    2015-01-01

    The FOXF1 (Forkhead box F1) gene, located on chromosome 16q24.1 encodes a member of the FOX family of tra